histocompatibility antigens class i

Summary

Summary: Large transmembrane, polymorphic glycoproteins noncovalently associated with nonpolymorphic beta 2-microglobulin. In humans, three structural genes on chromosome 6 code for the HLA-A; HLA-B and HLA-C antigens. In mice, three genes named K, D, and L on chromosome 17 code for the H-2 antigens. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during graft rejection and restrict cell-mediated lysis of virus-infected cells. They are primarily associated with rheumatologic diseases and certain malignant disorders.

Top Publications

  1. ncbi NK cell recognition
    Lewis L Lanier
    Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco School of Medicine, San Francisco, California 94143 0414, USA
    Annu Rev Immunol 23:225-74. 2005
  2. ncbi Sensitive and viable identification of antigen-specific CD8+ T cells by a flow cytometric assay for degranulation
    Michael R Betts
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892, USA
    J Immunol Methods 281:65-78. 2003
  3. ncbi How TCRs bind MHCs, peptides, and coreceptors
    Markus G Rudolph
    Department of Molecular Structural Biology, University of Gottingen, 37077 Gottingen, Germany
    Annu Rev Immunol 24:419-66. 2006
  4. ncbi FcRn: the neonatal Fc receptor comes of age
    Derry C Roopenian
    The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA
    Nat Rev Immunol 7:715-25. 2007
  5. pmc Structural insight into MR1-mediated recognition of the mucosal associated invariant T cell receptor
    Rangsima Reantragoon
    Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia
    J Exp Med 209:761-74. 2012
  6. ncbi The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells
    G B Cohen
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Immunity 10:661-71. 1999
  7. ncbi MHC class I molecules and KIRs in human history, health and survival
    Peter Parham
    Departments of Structural Biology, and Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA
    Nat Rev Immunol 5:201-14. 2005
  8. pmc Functional requirement for class I MHC in CNS development and plasticity
    G S Huh
    Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
    Science 290:2155-9. 2000
  9. ncbi In search of the 'missing self': MHC molecules and NK cell recognition
    H G Ljunggren
    Department of Tumour Biology, Karolinska Institutet, Stockholm, Sweden
    Immunol Today 11:237-44. 1990
  10. ncbi Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma
    Vinod Kumar
    Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
    Nat Genet 43:455-8. 2011

Research Grants

  1. CELLULAR ORIGINS OF RAT HEPATIC PRENEOPLASIAS
    Philip Iannaccone; Fiscal Year: 1991
  2. SIGNALLING THROUGH A T CELL KINASE, P56 LCK
    Andrey Shaw; Fiscal Year: 1992
  3. IMMUNOLOGICAL ENHANCEMENT OF RENAL ALLOGRAFTS
    FRANK STUART; Fiscal Year: 1980
  4. DECIDUAL CELL/PLACENTAL INTERACTIONS
    JOAN HUNT; Fiscal Year: 2007
  5. A Mouse Model of Gaucher Disease
    Ernest Beutler; Fiscal Year: 2005
  6. Iron Status: A Pathway Analysis in Multiple Ethnicities
    Christine McLaren; Fiscal Year: 2009
  7. Interactions and mechanisms of function of the TAP Complex
    Malini Raghavan; Fiscal Year: 2008
  8. Mycobacterium tuberculosis-reactive thymocytes
    MARIELLE GOLD; Fiscal Year: 2007
  9. Calreticulin's functions in the adaptive immune response
    Malini Raghavan; Fiscal Year: 2010
  10. Conference of the Society for Natural Immunity
    Wayne Yokoyama; Fiscal Year: 2005

Detail Information

Publications316 found, 100 shown here

  1. ncbi NK cell recognition
    Lewis L Lanier
    Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco School of Medicine, San Francisco, California 94143 0414, USA
    Annu Rev Immunol 23:225-74. 2005
    ..Here, I review the structure, function, and ligand specificity of the receptors responsible for NK cell recognition...
  2. ncbi Sensitive and viable identification of antigen-specific CD8+ T cells by a flow cytometric assay for degranulation
    Michael R Betts
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892, USA
    J Immunol Methods 281:65-78. 2003
    ....
  3. ncbi How TCRs bind MHCs, peptides, and coreceptors
    Markus G Rudolph
    Department of Molecular Structural Biology, University of Gottingen, 37077 Gottingen, Germany
    Annu Rev Immunol 24:419-66. 2006
    ..Notwithstanding, the impressive array of self, foreign (microbial), and autoimmune TCR complexes have uncovered the diverse ways in which antigens can be specifically recognized by TCRs...
  4. ncbi FcRn: the neonatal Fc receptor comes of age
    Derry C Roopenian
    The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA
    Nat Rev Immunol 7:715-25. 2007
    ..This Review summarizes these two areas of FcRn biology...
  5. pmc Structural insight into MR1-mediated recognition of the mucosal associated invariant T cell receptor
    Rangsima Reantragoon
    Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia
    J Exp Med 209:761-74. 2012
    ..This candidate docking mode contrasts with that of the NKT TCR-CD1d-antigen interaction, in which both the α and β chain of the NKT TCR is required for ligation above the F'-pocket of CD1d...
  6. ncbi The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells
    G B Cohen
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Immunity 10:661-71. 1999
    ..These results suggest that subpopulations of CTL and NK cells may be uniquely suited for combating HIV...
  7. ncbi MHC class I molecules and KIRs in human history, health and survival
    Peter Parham
    Departments of Structural Biology, and Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA
    Nat Rev Immunol 5:201-14. 2005
    ..Such correlations raise the possibility that interplay between KIR and MHC class I polymorphisms has facilitated human survival in the presence of epidemic infections and has influenced both reproduction and population growth...
  8. pmc Functional requirement for class I MHC in CNS development and plasticity
    G S Huh
    Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
    Science 290:2155-9. 2000
    ..These results demonstrate an important role for these molecules in the activity-dependent remodeling and plasticity of connections in the developing and mature mammalian central nervous system (CNS)...
  9. ncbi In search of the 'missing self': MHC molecules and NK cell recognition
    H G Ljunggren
    Department of Tumour Biology, Karolinska Institutet, Stockholm, Sweden
    Immunol Today 11:237-44. 1990
    ..The authors derive testable predictions for how MHC class I molecules act in cases where they control a rate-limiting step in the NK cell-target interaction...
  10. ncbi Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma
    Vinod Kumar
    Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
    Nat Genet 43:455-8. 2011
    ..13 × 10(-8)). We also found that the risk allele of rs2596542 was associated with lower soluble MICA protein levels in individuals with HCV-induced HCC (P = 1.38 × 10(-13))...
  11. ncbi A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis
    J N Feder
    Mercator Genetics, Inc, Menlo Park, California 94025, USA
    Nat Genet 13:399-408. 1996
    ..A role of this gene in haemochromatosis is supported by the frequency and nature of the major mutation and prior studies implicating MHC class I-like proteins in iron metabolism...
  12. ncbi Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA
    S Bauer
    Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Avenue North, Seattle, WA 98109, USA
    Science 285:727-9. 1999
    ..These results define an activating immunoreceptor-MHC ligand interaction that may promote antitumor NK and T cell responses...
  13. ncbi Antimicrobial activity of mucosal-associated invariant T cells
    Lionel Le Bourhis
    Departement de Biologie des Tumeurs, Institut Curie, Paris, France
    Nat Immunol 11:701-8. 2010
    ..In the mouse, MAIT cells protected against infection by Mycobacterium abscessus or Escherichia coli. Thus, MAIT cells are evolutionarily conserved innate-like lymphocytes that sense and help fight off microbial infection...
  14. pmc Stepwise development of MAIT cells in mouse and human
    Emmanuel Martin
    Laboratoire d Immunologie, Institut Curie, Paris, France
    PLoS Biol 7:e54. 2009
    ..Thus, their development follows a unique pattern at the crossroad of NKT and gammadelta T cells...
  15. pmc NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8-11
    Claus Lundegaard
    CBS, Department of Systems Biology, Technical University of Denmark DTU, Kemitorvet Build 208, 2800 Lyngby, Denmark
    Nucleic Acids Res 36:W509-12. 2008
    ..Here, the performance is further validated and benchmarked using a large set of newly published affinity data, non-redundant to the training set. The server is free of use and available at: http://www.cbs.dtu.dk/services/NetMHC...
  16. ncbi A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol
    Yihong Ye
    Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 429:841-7. 2004
    ..Derlin-1 interacts with US11, a virally encoded ER protein that specifically targets MHC class I heavy chains for export from the ER, as well as with VIMP, a novel membrane protein that recruits the p97 ATPase and its cofactor...
  17. ncbi Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis
    A Moretta
    Dipartimento di Medicina Sperimentale, Universita degli Studi di Genova, Italy
    Annu Rev Immunol 19:197-223. 2001
    ..Indeed, in patients with the X-linked lymphoproliferative disease, the inability to control Epstein-Barr virus infections may be consequent to a major dysfunction of 2B4 that exerts inhibitory instead of activating functions...
  18. ncbi Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation
    Veronika Groh
    Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Avenue North, Seattle, Washington 98109, USA
    Nature 419:734-8. 2002
    ..This mode of T-cell silencing may promote tumour immune evasion and, by inference, compromise host resistance to infections...
  19. pmc Effect of NKG2D ligand expression on host immune responses
    Marine Champsaur
    Department of Microbiology and Immunology, The Biomedical Sciences Graduate Program and The Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143, USA
    Immunol Rev 235:267-85. 2010
    ..We also discuss the host response to both membrane-bound and secreted NKG2D ligands and summarize the models proposed to explain the consequences of this differential expression...
  20. ncbi Recognition of stress-induced MHC molecules by intestinal epithelial gammadelta T cells
    V Groh
    Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Avenue North, Seattle, WA 98109, USA
    Science 279:1737-40. 1998
    ..Thus, these molecules may broadly regulate protective responses by the Vdelta1 gammadelta T cells in the epithelium of the intestinal tract...
  21. pmc Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB
    V Groh
    Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Avenue North, Seattle, WA 98109, USA
    Proc Natl Acad Sci U S A 96:6879-84. 1999
    ..These results raise the possibility that an induced expression of MICA/B, by conditions that may be related to tumor homeostasis and growth, could play a role in immune responses against tumors...
  22. ncbi Natural selection at major histocompatibility complex loci of vertebrates
    A L Hughes
    Department of Biology, Pennsylvania State University, University Park 16802, USA
    Annu Rev Genet 32:415-35. 1998
    ..d) Introns have been homogenized relative to exons over evolutionary time, suggesting that balancing selection acts to maintain diversity in the latter, in contrast to the former...
  23. ncbi Mucosal-associated invariant T cells: unconventional development and function
    Lionel Le Bourhis
    Institut Curie, Departement de Biologie des Tumeurs, Paris, 75005, France
    Trends Immunol 32:212-8. 2011
    ..MAIT cells secrete interferon-γ, and interleukin-17 under certain conditions. The species conservation, as well as the wide microbial reactivity, infer an important role for this cell population in immunity...
  24. pmc Endogenous naive CD8+ T cell precursor frequency regulates primary and memory responses to infection
    Joshua J Obar
    Department of Immunology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington CT 06030 1319, USA
    Immunity 28:859-69. 2008
    ..Thus, initial endogenous precursor frequencies were surprisingly diverse and not only regulated initial immune response characteristics but also controlled memory CD8+ T cell lineage decisions...
  25. pmc MHC class I: an unexpected role in neuronal plasticity
    Carla J Shatz
    Bio X and Departments of Biology and Neurobiology, James H Clark Center, 318 Campus Drive W1 1, Stanford University, Stanford CA 94305 5437, USA
    Neuron 64:40-5. 2009
    ....
  26. ncbi Costimulation of CD8alphabeta T cells by NKG2D via engagement by MIC induced on virus-infected cells
    V Groh
    Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA 98109, USA
    Nat Immunol 2:255-60. 2001
    ..Combined triggering of TCR-CD3 complexes and NKG2D induced interleukin 2 production and T cell proliferation. Thus NKG2D functioned as a costimulatory receptor that can substitute for CD28...
  27. pmc Mamu-B*08-positive macaques control simian immunodeficiency virus replication
    John T Loffredo
    Wisconsin National Primate Research Center, University of Wisconsin Madison, 555 Science Drive, Madison, WI 53711, USA
    J Virol 81:8827-32. 2007
    ..002). Mamu-B*08-positive macaques may, therefore, provide a good model to understand the correlates of MHC class I allele-associated immune protection and viral containment in human elite controllers...
  28. pmc CD8(+) T cells: foot soldiers of the immune system
    Nu Zhang
    Department of Immunology and the Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA
    Immunity 35:161-8. 2011
    ..Here we review recent advances in CD8(+) T cell recognition of antigen in lymphoid as well as in nonlymphoid tissues in the periphery, and how CD8(+) T cell expansion and differentiation are controlled in these contexts...
  29. pmc Characterization of the expression of MHC proteins in human embryonic stem cells
    Micha Drukker
    Department of Genetics, Silberman Institute of Life Sciences, Hebrew University, 91904 Jerusalem, Israel
    Proc Natl Acad Sci U S A 99:9864-9. 2002
    ..In conclusion, our results demonstrate that human ES cells can express high levels of MHC-I proteins and thus may be rejected on transplantation...
  30. pmc Evasion of CD8+ T cells is critical for superinfection by cytomegalovirus
    Scott G Hansen
    Vaccine and Gene Therapy Institute, Oregon Health and Science University, 505 Northwest 185th Avenue, Beaverton, OR 97006, USA
    Science 328:102-6. 2010
    ....
  31. ncbi MHC class I antigen presentation: learning from viral evasion strategies
    Ted H Hansen
    Washington University School of Medicine, Department of Pathology and Immunology, St Louis, Missouri 63110, USA
    Nat Rev Immunol 9:503-13. 2009
    ....
  32. pmc A human histocompatibility leukocyte antigen (HLA)-G-specific receptor expressed on all natural killer cells
    S Rajagopalan
    Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA
    J Exp Med 189:1093-100. 1999
    ..Therefore, given that HLA-G expression is restricted to fetal trophoblast cells, KIR2DL4 may provide important signals to maternal NK decidual cells that interact with trophoblast cells at the maternal-fetal interface during pregnancy...
  33. ncbi Natural killer cells and dendritic cells: rendezvous in abused tissues
    Alessandro Moretta
    Dipartimento di Medicina Sperimentale, Sezione di Istologia, and Centro di Eccellenza per le Ricerche Biomediche, Universita degli Studi di Genova, 16132 Genova, Italy
    Nat Rev Immunol 2:957-64. 2002
    ....
  34. ncbi Cytomegalovirus immune evasion
    C Powers
    Vaccine and Gene Therapy Institute, Oregon Health and Science University, Portland, OR 97201, USA
    Curr Top Microbiol Immunol 325:333-59. 2008
    ..The multitude and complexity of these mechanisms is fascinating and continues to reveal novel insights into the host-pathogen interaction and novel cell biological and immunological concepts...
  35. pmc Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes
    Mark E Dudley
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20902, USA
    Science 298:850-4. 2002
    ..This approach presents new possibilities for the treatment of patients with cancer as well as patients with human immunodeficiency virus-related acquired immunodeficiency syndrome and other infectious diseases...
  36. pmc HLA-E expression by gynecological cancers restrains tumor-infiltrating CD8⁺ T lymphocytes
    Marloes Gooden
    Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
    Proc Natl Acad Sci U S A 108:10656-61. 2011
    ....
  37. ncbi Association of HFE and TMPRSS6 genetic variants with iron and erythrocyte parameters is only in part dependent on serum hepcidin concentrations
    Michela Traglia
    Division of Genetics and Cell Biology, San Raffaele Research Institute, Milano, Italy
    J Med Genet 48:629-34. 2011
    ..Hepcidin is the main regulator of iron homeostasis: inappropriate production of hepcidin results in iron overload or iron deficiency and anaemia...
  38. ncbi KIR: diverse, rapidly evolving receptors of innate and adaptive immunity
    Carlos Vilches
    Servicio de Inmunologia, Hospital Universitario Clinica Puerta de Hierro, San Martin de Porres 4, 28035 Madrid, Spain
    Annu Rev Immunol 20:217-51. 2002
    ..This diversity likely contributes variability to the function of NK cells and T-lymphocytes by modulating innate and adaptive immune responses to specific challenges...
  39. ncbi Natural killer cells efficiently reject lymphoma silenced for the endoplasmic reticulum aminopeptidase associated with antigen processing
    Loredana Cifaldi
    Oncohaematology Department, IRCCS, Ospedale Pediatrico Bambino Gesu, Rome, Italy
    Cancer Res 71:1597-606. 2011
    ..Because a large fraction of human tumors express high levels of the homologous ERAP1 and/or ERAP2, the present findings highlight a convenient, novel target for cancer immunotherapy...
  40. ncbi Modulation of HLA expression in human cytomegalovirus immune evasion
    Aifen Lin
    Medical Research Center, Wenzhou Medical College Affiliated Taizhou Hospital of Zhejiang Province, Linhai, Zhejiang 317000, China
    Cell Mol Immunol 4:91-8. 2007
    ....
  41. ncbi Licensing of natural killer cells by host major histocompatibility complex class I molecules
    Sungjin Kim
    Howard Hughes Medical Institute, Rheumatology Division, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Nature 436:709-13. 2005
    ..This self-tolerance mechanism may be more broadly applicable within the vertebrate immune system because related germline-encoded inhibitory receptors are widely expressed on other immune cells...
  42. ncbi Immune regulation by pretenders: cell-to-cell transfers of HLA-G make effector T cells act as regulatory cells
    Joel Lemaoult
    Service de Recherches en Hemato Immunologie, Commissariat à l Energie Atomique CEA DSV DRM, Institut Universitaire d Hematologie, Hopital Saint Louis, Paris, France
    Blood 109:2040-8. 2007
    ..These data re-emphasize the significance of HLA-G expression in normal and pathologic situations...
  43. pmc Transgenic mice lacking class I major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge
    B S Bender
    Department of Medicine, University of Florida College of Medicine, Gainesville
    J Exp Med 175:1143-5. 1992
    ..Thus, CD8+ T cells are important in recovery from virulent influenza infections, but other host defense mechanisms can clear the respiratory tract of more benign infections...
  44. pmc Modulation of different human immunodeficiency virus type 1 Nef functions during progression to AIDS
    S Carl
    Institute for Clinical and Molecular Virology, Friedrich-Alexander University, D-91054 Erlangen, Germany
    J Virol 75:3657-65. 2001
    ..These findings suggest that all in vitro Nef functions investigated contribute to AIDS pathogenesis and indicate that nef variants with increased pathogenicity emerge in a significant number of HIV-1-infected individuals...
  45. ncbi Regulation of cutaneous malignancy by gammadelta T cells
    M Girardi
    Department of Dermatology and Yale Skin Diseases Research Core Center, King s College, London SE1 9RT, UK
    Science 294:605-9. 2001
    ..Thus, local T cells may use evolutionarily conserved proteins to negatively regulate malignancy...
  46. ncbi Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1
    Emmanuel Treiner
    Laboratoire d Immunologie and INSERM U520, Institut Curie, Paris 75005, France
    Nature 422:164-9. 2003
    ..This indicates that MAIT cells are probably involved in the host response at the site of pathogen entry, and may regulate intestinal B-cell activity...
  47. pmc HLA class I antigen processing machinery component expression and intratumoral T-Cell infiltrate as independent prognostic markers in ovarian carcinoma
    Liz Y Han
    Department of Gynecologic Oncology, The University of Texas M D Anderson Cancer Center, 1155 Herman Pressler, CPB6 3244, Unit 1362, Houston, TX 77030, USA
    Clin Cancer Res 14:3372-9. 2008
    ..The purpose of this study is to determine the clinical significance of APM component down-regulation and tumor-infiltrating T cells in ovarian carcinoma...
  48. pmc Unravelling natural killer cell function: triggering and inhibitory human NK receptors
    Lorenzo Moretta
    Istituto Giannina Gaslini, Genova Quarto, Italy
    EMBO J 23:255-9. 2004
    ..Thus, the ability of NK cells to lyse target cells requires both the lack of surface MHC class I molecules and the expression of appropriate ligands that trigger NK receptors...
  49. pmc HLA-G1-expressing antigen-presenting cells induce immunosuppressive CD4+ T cells
    Joel Lemaoult
    Service de Recherches en Hemato Immunologie, Commissariat à l Energie Atomique Département de Recherche Médicale Direction des Sciences du Vivant, Hopital Saint Louis, 1 avenue Claude Vellefaux, 75475 Paris 10, France
    Proc Natl Acad Sci U S A 101:7064-9. 2004
    ..Thus, HLA-G+ APCs might (i) be involved in the direct suppression of immune responses and (ii) contribute to long-term efficient immune escape or tolerance...
  50. ncbi Therapeutic induction of regulatory, cytotoxic CD8+ T cells in multiple sclerosis
    Deepani K Tennakoon
    Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    J Immunol 176:7119-29. 2006
    ..These studies not only explain several prior observations relating to the mechanism of this drug but also provide important insights into the natural immune interplay underlying this human immune-mediated disease...
  51. ncbi Interferon-gamma, the functional plasticity of the ubiquitin-proteasome system, and MHC class I antigen processing
    Britta Strehl
    Institut fur Biochemie, Charite, Berlin University Berlin, Germany
    Immunol Rev 207:19-30. 2005
    ....
  52. pmc Conditional deletion of the MHC class I-related receptor FcRn reveals the sites of IgG homeostasis in mice
    Héctor Pérez Montoyo
    Department of Immunology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390 9093, USA
    Proc Natl Acad Sci U S A 106:2788-93. 2009
    ..The primary sites for the maintenance of endogenous IgGs in mice are therefore endothelial and hematopoietic cells...
  53. pmc Major histocompatibility complex genotyping with massively parallel pyrosequencing
    Roger W Wiseman
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, Wisconsin, USA
    Nat Med 15:1322-6. 2009
    ..The remarkable sensitivity of this approach in macaques demonstrates that pyrosequencing is viable for ultra-high-throughput MHC genotyping of primates, including humans...
  54. ncbi Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein
    O Schwartz
    Laboratoire Rétrovirus et Transfert Génétique, Unité de Recherche Associée CNRS 1157, Paris, France
    Nat Med 2:338-42. 1996
    ..The stimulation of MHC-I endocytosis by Nef represents a previously undocumented viral mechanism for evading the immune response...
  55. pmc Structural basis for recognition of the nonclassical MHC molecule HLA-G by the leukocyte Ig-like receptor B2 (LILRB2/LIR2/ILT4/CD85d)
    Mitsunori Shiroishi
    Division of Structural Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
    Proc Natl Acad Sci U S A 103:16412-7. 2006
    ..These results suggest that subtle structural differences between LILRB family members cause the distinct binding specificities to various forms of HLA-G and other MHCIs, which may in turn regulate immune suppression...
  56. ncbi A novel immunoglobulin superfamily receptor for cellular and viral MHC class I molecules
    D Cosman
    Immunex Corporation, Seattle, Washington 98101, USA
    Immunity 7:273-82. 1997
    ..Upon tyrosine phosphorylation, LIR-1 associates with the tyrosine phosphatase SHP-1. In contrast to KIRs, LIR-1 is expressed predominantly on monocytic and B lymphoid cell types, suggesting a distinct biological function...
  57. ncbi Important role of cathepsin S in generating peptides for TAP-independent MHC class I crosspresentation in vivo
    Lianjun Shen
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    Immunity 21:155-65. 2004
    ..Therefore, cathepsin S plays a major role in generating presented peptides for the vacuolar pathway of crosspresentation, and this mechanism is active in vivo...
  58. ncbi Analysis of regulatory CD8 T cells in Qa-1-deficient mice
    Dan Hu
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Immunol 5:516-23. 2004
    ..These findings delineate a Qa-1-dependent T cell-T cell inhibitory interaction that prevents the pathogenic expansion of autoreactive CD4 T cell populations and consequent autoimmune disease...
  59. ncbi Proteasome and peptidase function in MHC-class-I-mediated antigen presentation
    Peter Michael Kloetzel
    Institut fur Biochemie, Charité Medizinische Fakultät der Humboldt Universität zu Berlin, Monbijoustrasse 2, 10117 Berlin, Germany
    Curr Opin Immunol 16:76-81. 2004
    ..Recent evidence suggests that tripeptidyl peptidase II (TPPII), a large peptidase with exo-and endo-proteolytic activities, is also involved in antigen processing and may generate a specific set of MHC class I epitopes...
  60. ncbi A T cell receptor flattens a bulged antigenic peptide presented by a major histocompatibility complex class I molecule
    Fleur E Tynan
    Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia
    Nat Immunol 8:268-76. 2007
    ..Our findings represent a mechanism of antigen recognition whereby the plasticity of the T cell response is dictated mainly by adjustments in the MHC-bound peptide...
  61. ncbi An IFN-gamma-induced aminopeptidase in the ER, ERAP1, trims precursors to MHC class I-presented peptides
    Tomo Saric
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Nat Immunol 3:1169-76. 2002
    ..Like other proteins involved in antigen presentation, ERAP1 is induced by interferon-gamma. When overexpressed in vivo, we found that ERAP1 stimulates the processing and presentation of an antigenic precursor in the ER...
  62. pmc Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G
    Mitsunori Shiroishi
    Division of Structural Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
    Proc Natl Acad Sci U S A 100:8856-61. 2003
    ....
  63. ncbi Imprint of human cytomegalovirus infection on the NK cell receptor repertoire
    Monica Guma
    Molecular Immunopathology Unit, DCEXS, Universitat Pompeu Fabra, Barcelona, Spain
    Blood 104:3664-71. 2004
    ..Altogether, these data support that HCMV infection selectively shapes the natural killer cell receptor (NKR) repertoire of NK and T cells from healthy carrier individuals...
  64. ncbi A hybrid approach for predicting promiscuous MHC class I restricted T cell epitopes
    Manoj Bhasin
    Institute of Microbial Technology, Sector 39A, Chandigarh 160 036, India
    J Biosci 32:31-42. 2007
    ..The method is available on the web at www.imtech.res.in/raghava/nhlapred and its mirror site is available at http://bioinformatics.uams.edu/mirror/nhlapred/...
  65. ncbi ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum
    Thomas Serwold
    Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720 3200, USA
    Nature 419:480-3. 2002
    ..Thus, ERAAP is the missing link between the products of cytosolic processing and the final peptides presented by MHC class I molecules on the cell surface...
  66. ncbi Crystal structure at 2.8 A of an FcRn/heterodimeric Fc complex: mechanism of pH-dependent binding
    W L Martin
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Mol Cell 7:867-77. 2001
    ..The structure reveals conformational changes in Fc and three titratable salt bridges that confer pH-dependent binding, and can be used to guide rational design of therapeutic IgGs with longer serum half-lives...
  67. pmc Thymic selection determines gammadelta T cell effector fate: antigen-naive cells make interleukin-17 and antigen-experienced cells make interferon gamma
    Kirk D C Jensen
    Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA
    Immunity 29:90-100. 2008
    ..The swift IL-17 response mounted by antigen-naive gammadelta T cells suggests a critical role for these cells at the onset of an acute inflammatory response to novel antigens...
  68. pmc The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding
    J N Feder
    Progenitor, Inc formerly Mercator Genetics, Inc, 4040 Campbell Avenue, Menlo Park, CA 94025, USA
    Proc Natl Acad Sci U S A 95:1472-7. 1998
    ....
  69. ncbi Human myelomonocytic cells express an inhibitory receptor for classical and nonclassical MHC class I molecules
    M Colonna
    Basel Institute for Immunology, Switzerland
    J Immunol 160:3096-100. 1998
    ..ILT4 may control inflammatory responses and cytotoxicity mediated by myelomonocytic cells and may modulate their Ag-presenting functions, focusing immune responses to microbial challenges and avoiding autoreactivity...
  70. ncbi Differences in promiscuity for antibody-FcRn interactions across species: implications for therapeutic antibodies
    R J Ober
    Cancer Immunobiology Center and Center for Immunology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390 8576, USA
    Int Immunol 13:1551-9. 2001
    ..Our results provide a molecular explanation for the enigmatic observation that mouse IgG behave anomalously in humans. These studies have implications for the successful application of therapeutic antibodies...
  71. pmc Neonatal Fc receptor for IgG (FcRn) regulates cross-presentation of IgG immune complexes by CD8-CD11b+ dendritic cells
    Kristi Baker
    Division of Gastroenterology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 108:9927-32. 2011
    ..Given the centrality of FcRn in controlling cross-presentation, these studies lay the foundation for a unique means to therapeutically manipulate CD8(+) T-cell responses...
  72. pmc The transferrin receptor modulates Hfe-dependent regulation of hepcidin expression
    Paul J Schmidt
    Division of Hematology Oncology, Children s Hospital Boston, Boston, MA 02115, USA
    Cell Metab 7:205-14. 2008
    ..Together, these models suggest that Hfe induces hepcidin expression when it is not in complex with Tfr1...
  73. pmc HLA-E-restricted regulatory CD8(+) T cells are involved in development and control of human autoimmune type 1 diabetes
    Hong Jiang
    Department of Medicine, Naomi Berrie Diabetes Center NBDC, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA
    J Clin Invest 120:3641-50. 2010
    ..These data suggest that HLA-E-restricted CD8(+) T cells may play an important role in keeping self-reactive T cells in check. Thus, correction of this defect could be a potentially effective and safe approach in the therapy of T1D...
  74. pmc Regulation of activated CD4+ T cells by NK cells via the Qa-1-NKG2A inhibitory pathway
    Linrong Lu
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Immunity 26:593-604. 2007
    ....
  75. pmc Podocytes use FcRn to clear IgG from the glomerular basement membrane
    Shreeram Akilesh
    Department of Pathology and Immunology, Renal Division, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 105:967-72. 2008
    ....
  76. ncbi Engineering human IgG1 affinity to human neonatal Fc receptor: impact of affinity improvement on pharmacokinetics in primates
    Yik Andy Yeung
    Department of Antibody Engineering, Genentech, South San Francisco, CA 94080, USA
    J Immunol 182:7663-71. 2009
    ..In contrast, N434A exhibited a approximately 2-fold decrease in clearance in cynomolgus monkey, supporting the notion that modest increases in pH 6 FcRn affinity can result in improved pharmacokinetics in primates...
  77. ncbi Herpes simplex virus infection downmodulates NKG2D ligand expression
    D Schepis
    Department of Microbiology, Tumor and Cell Biology and Strategic Research Center IRIS, Karolinska Institutet, Stockholm, Sweden
    Scand J Immunol 69:429-36. 2009
    ..These data support a role for NKG2D-MICA interactions in immune responses to HSV-1 reactivation...
  78. ncbi Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-G pathway
    Silvia Gregori
    Department of Regenerative Medicine, Stem Cells, and Gene Therapy, San Raffaele Telethon Institute for Gene Therapy, Via Olgettina 58, Milan, Italy
    Blood 116:935-44. 2010
    ..Our data indicate that DC-10 represents a novel subset of tolerogenic DCs, which secrete high levels of IL-10, express ILT4 and HLA-G, and have the specific function to induce Tr1 cells...
  79. ncbi Soluble HLA-G inhibits cell cycle progression in human alloreactive T lymphocytes
    Rajia Bahri
    Institut National de la Santé et de la Recherche Médicale Unité 542, Villejuif, France
    J Immunol 176:1331-9. 2006
    ..In contrast, it induced an accumulation of p27kip, but not p21cip, in activated T cells. HLA-G does not induce apoptosis of alloreactive T cells, but induces p27kip1 and inhibits cell cycle progression...
  80. ncbi Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum
    Loredana Saveanu
    Institut National de la Sante et Recherche Médicale Unité 580, Universite Rene Descartes Paris 5, 75015 Paris, France
    Nat Immunol 6:689-97. 2005
    ..Thus, the human endoplasmic reticulum is equipped with a pair of trimming aminopeptidases that have complementary functions in HLA class I peptide presentation...
  81. ncbi HLA-G: from biology to clinical benefits
    Edgardo D Carosella
    Institut Universitaire d Hematologie, Service de Recherches en Hemato Immunologie, Hopital Saint Louis, IUH, 1 75010 Paris, France
    Trends Immunol 29:125-32. 2008
    ..These recent findings are important in terms of clinical benefits at both diagnostic and therapeutic levels...
  82. pmc A statistical method for predicting classical HLA alleles from SNP data
    Stephen Leslie
    Department of Statistics, University of Oxford, Oxford OX1 3TG, UK
    Am J Hum Genet 82:48-56. 2008
    ....
  83. ncbi ProPred1: prediction of promiscuous MHC Class-I binding sites
    Harpreet Singh
    Institute of Microbial Technology, Chandigarh 160036, India
    Bioinformatics 19:1009-14. 2003
    ..The simultaneous prediction of MHC binders and proteasome cleavage sites in an antigenic sequence leads to the identification of potential T-cell epitopes...
  84. pmc Soluble HLA-G protein secreted by allo-specific CD4+ T cells suppresses the allo-proliferative response: a CD4+ T cell regulatory mechanism
    N Lila
    , , Direction des Sciences du Vivant, , , 1 avenue Claude-Vellefaux, 75010 Paris, France
    Proc Natl Acad Sci U S A 98:12150-5. 2001
    ..This inhibition may be reversed by adding the anti-HLA-G 87G antibody to a mixed lymphocyte culture. That may indicate a previously uncharacterized regulatory mechanism of CD4(+) T cell proliferative response...
  85. ncbi Antibodies against MICA antigens and kidney-transplant rejection
    Yizhou Zou
    Transplantation Immunology Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 8886, USA
    N Engl J Med 357:1293-300. 2007
    ..We sought to determine whether an immune response to MICA antigens might play a role in the failure of kidney allografts...
  86. pmc Alternative splicing of HLA-G transcripts yields proteins with primary structures resembling both class I and class II antigens
    A Ishitani
    Fred Hutchinson Cancer Research Center, Seattle, WA 98104 2092
    Proc Natl Acad Sci U S A 89:3947-51. 1992
    ..These findings are discussed in terms of potential functions of the alternative HLA-G proteins...
  87. pmc Disulfide bond-mediated dimerization of HLA-G on the cell surface
    Jonathan E Boyson
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138 and Institute of Molecular Genetics, 142 20 Prague, Czech Republic
    Proc Natl Acad Sci U S A 99:16180-5. 2002
    ..The cell-surface expression of dimerized HLA-G molecules may have implications for HLA-Greceptor interactions and for the search for specific receptors that bind HLA-G...
  88. ncbi HLA-G and immune tolerance in pregnancy
    Joan S Hunt
    Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas 66160 7400, USA
    FASEB J 19:681-93. 2005
    ....
  89. ncbi Host immune system gene targeting by a viral miRNA
    Noam Stern-Ginossar
    Lautenberg Center for General and Tumor Immunology, Hebrew University Hadassah Medical School, Jerusalem, Israel
    Science 317:376-81. 2007
    ..Our results reveal a miRNA-based immunoevasion mechanism that appears to be exploited by human cytomegalovirus...
  90. pmc Down-regulation of NKG2D and NKp80 ligands by Kaposi's sarcoma-associated herpesvirus K5 protects against NK cell cytotoxicity
    Mair Thomas
    Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge, Hills Road, Cambridge CB2 0XY, United Kingdom
    Proc Natl Acad Sci U S A 105:1656-61. 2008
    ..The down-regulation of ligands for both the NKG2D and NKp80 activation pathways provides KSHV with a powerful mechanism for evasion of NK cell antiviral functions...
  91. pmc SEL1L, the homologue of yeast Hrd3p, is involved in protein dislocation from the mammalian ER
    Britta Mueller
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    J Cell Biol 175:261-70. 2006
    ..These results allow us to place SEL1L in the broader context of glycoprotein degradation, and imply the existence of multiple independent modes of extraction of misfolded substrates from the mammalian ER...
  92. ncbi Tolerization of dendritic cells by HLA-G
    Vladimir Ristich
    Institute of Molecular Medicine and Genetics, Department of Medicine, Medical College of Georgia, Augusta 30912 2600, USA
    Eur J Immunol 35:1133-42. 2005
    ..These findings provide support that HLA-G is an important tolerogenic molecule on DC for the acceptance of a semiallogeneic fetus and transplanted tissue/organ...
  93. ncbi Beyond the increasing complexity of the immunomodulatory HLA-G molecule
    Edgardo D Carosella
    CEA, IBM, Service de Recherches en Hemato Immunologie, Paris, France
    Blood 111:4862-70. 2008
    ..We highlight here what we consider are recent key basic findings on the immunomodulatory function of HLA-G. These strengthen the case for considering HLA-G as clinically relevant...
  94. ncbi Hypoxia modulates HLA-G gene expression in tumor cells
    Gael Mouillot
    Commissariat a l Energie Atomique, Service de Recherches en Hemato Immunologie, Direction des Sciences du Vivant Dèpartement de Recherche Médicale, Hopital Saint Louis, Institut Universitaire d Hematologie, Paris, France
    Hum Immunol 68:277-85. 2007
    ..Finally, we demonstrated for the first time that the modulation of HLA-G gene expression is dependent of HIF-1 stabilization and thus might be relevant for the control of HLA-G gene expression in hypoxic tumors...
  95. ncbi Structure of 20S proteasome from yeast at 2.4 A resolution
    M Groll
    Max Planck Institut fur Biochemie, Martinsreid, Germany
    Nature 386:463-71. 1997
    ....
  96. pmc Distinct migrating and nonmigrating dendritic cell populations are involved in MHC class I-restricted antigen presentation after lung infection with virus
    Gabrielle T Belz
    Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
    Proc Natl Acad Sci U S A 101:8670-5. 2004
    ..Presentation by a nonairway-derived DC population argues that cytotoxic T lymphocyte priming may involve interplay between different DC subsets, not all of which originate within the site of infection...
  97. ncbi "Hard" and "soft" lesions underlying the HLA class I alterations in cancer cells: implications for immunotherapy
    Federico Garrido
    Departamento de Bioquimica, Universidad de Granada, Granada, Spain
    Int J Cancer 127:249-56. 2010
    ..In this article, we discuss the importance of these two types of molecular mechanisms of MHC Class I-altered expression...
  98. ncbi Down-regulation of the NKG2D ligand MICA by the human cytomegalovirus glycoprotein UL142
    N Jan Chalupny
    Amgen, 1201 Amgen Court West, Seattle, WA 98119 3105, USA
    Biochem Biophys Res Commun 346:175-81. 2006
    ....
  99. pmc Thermal- and oxidative stress causes enhanced release of NKG2D ligand-bearing immunosuppressive exosomes in leukemia/lymphoma T and B cells
    Malin Hedlund
    Division of Clinical Immunology, Department of Clinical Microbiology, Umea University, Umea, Sweden
    PLoS ONE 6:e16899. 2011
    ..The adverse effect of thermal and oxidative stress, enhancing the release of immunosuppressive exosomes, should be considered when cytostatic and hyperthermal anti-cancer therapies are designed...
  100. pmc High expression of HLA-E in colorectal carcinoma is associated with a favorable prognosis
    Maria Benevolo
    Department of Pathology, Regina Elena National Cancer Institute, Via E Chianesi 53, 00144 Rome, Italy
    J Transl Med 9:184. 2011
    ..In view of the opposing outcomes (activation or inhibition) of the different HLA-E receptors, the preferred role (if any) of HLA-E expressed in vivo on tumor cells remains to be established...
  101. pmc Neonatal Fc receptor: from immunity to therapeutics
    Timothy T Kuo
    Division of Gastroenterology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA
    J Clin Immunol 30:777-89. 2010
    ..Here, we aim to summarize the basic understanding of FcRn biology, its functions in various organs, and the therapeutic design of antibody- and albumin-based therapeutics in light of their interactions with FcRn...

Research Grants68

  1. CELLULAR ORIGINS OF RAT HEPATIC PRENEOPLASIAS
    Philip Iannaccone; Fiscal Year: 1991
    ....
  2. SIGNALLING THROUGH A T CELL KINASE, P56 LCK
    Andrey Shaw; Fiscal Year: 1992
    ..Aberrant signalling through CD4 could play a role in HIV pathogenesis. ..
  3. IMMUNOLOGICAL ENHANCEMENT OF RENAL ALLOGRAFTS
    FRANK STUART; Fiscal Year: 1980
    ..We will also combine various effective supernatants in an attempt to achieve enhancement without the need for concomitant donor strain spleen cells. ..
  4. DECIDUAL CELL/PLACENTAL INTERACTIONS
    JOAN HUNT; Fiscal Year: 2007
    ..abstract_text> ..
  5. A Mouse Model of Gaucher Disease
    Ernest Beutler; Fiscal Year: 2005
    ..In particular, electron microscopy and light microscopy will be used to attempt to demonstrate the development of Gaucher cells in the chimeric mice. ..
  6. Iron Status: A Pathway Analysis in Multiple Ethnicities
    Christine McLaren; Fiscal Year: 2009
    ..Potential study results could be used to identify individuals at risk for iron deficiency and to develop innovative prevention and treatment strategies. ..
  7. Interactions and mechanisms of function of the TAP Complex
    Malini Raghavan; Fiscal Year: 2008
    ..abstract_text> ..
  8. Mycobacterium tuberculosis-reactive thymocytes
    MARIELLE GOLD; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  9. Calreticulin's functions in the adaptive immune response
    Malini Raghavan; Fiscal Year: 2010
    ..Understanding the molecular mechanisms of calreticulin's functions, and elucidation of conditions that enhance calreticulin's T cell priming activities, will facilitate more effective design of vaccines. ..
  10. Conference of the Society for Natural Immunity
    Wayne Yokoyama; Fiscal Year: 2005
    ..abstract_text> ..
  11. Ocular Regulation of Autoimmunity
    ROBERT CONE; Fiscal Year: 2009
    ..The results of this study could aid our understanding of the systemic basis for the ocular regulation of autoimmunity and develop procedures for the modulation of active autoimmune disease. ..
  12. DNA Methylation as an Epigenetic Host Factor in HIV/AIDS
    Jianming Tang; Fiscal Year: 2006
    ..abstract_text> ..
  13. Conference on Innate Immunity to Pathogens
    Wayne Yokoyama; Fiscal Year: 2005
    ..abstract_text> ..
  14. MOLECULAR MODEL FOR T-CELL RECEPTOR LIGAND INTERACTIONS
    Nilabh Shastri; Fiscal Year: 2007
    ..We expect the findings to reveal new insights into the nature of endogenous peptides presented by MHC class II and MHC class I molecules in normal cells as well as fundamental issues in transplantation immunology. ..
  15. VIRAL EVASION STRATEGIES: ANALYSIS OF HERPES VIRUSES HSV, VZV AND HHV-6-7
    Hidde Ploegh; Fiscal Year: 2007
    ..This analysis should reveal if and to what extent the MHC alleles in the human population help shape the "repertoire" of immunoevasins. ..
  16. Functional Proteomics of HIV-1-Specific CD8+ T cells
    Xu Yu; Fiscal Year: 2007
    ..Overall, our investigations will be relevant for defining key signaling networks of HI V-1-specific CD8+ T cells associated with protective immunity against HIV-1. [unreadable] [unreadable]..
  17. CD8+ T Cells Control Autoimmunity In EAE
    Hong Jiang; Fiscal Year: 2007
    ..Thus, the studies will provide theoretical basis for clinical application of this regulatory pathway in prevention and treatment of multiple sclerosis in man. [unreadable] [unreadable] [unreadable]..
  18. Antigen processing in the secretory pathway
    Nilabh Shastri; Fiscal Year: 2010
    ..abstract_text> ..
  19. ROLE OF NON-CLASSICAL MHC CLASS I AND HSPs IN IMMUNITY
    Jacques Robert; Fiscal Year: 2009
    ..Do hsp70 and gp96 generate similar anti-tumor CCU-CTL effectors? Aim 3. How important is the hsp-generated CCU-CTL responses in tumor immunity in vivo? Aim 4. Do CCU-CTLs interact with class Ib molecules? ..
  20. Thymic Influence on Ocular Immunoregulation
    Robert E Cone; Fiscal Year: 2010
    ....
  21. The genetic basis of type 1 diabetes autoimmunity in African Americans
    Janelle Noble; Fiscal Year: 2008
    ..abstract_text> ..
  22. Genetic Epidemiology of Adult Brain Cancer: A Follow-up Study
    Jianming Tang; Fiscal Year: 2008
    ..abstract_text> ..
  23. Regulation of the baboon HLA-G-like class Ib MHC gene, Paan-AG
    DAUDI LANGAT; Fiscal Year: 2008
    ..Thus the baboon is clearly an excellent model for HLA-G functional experiments, and testing the therapeutic applications of HLA-G in human pregnancy and transplantation. [unreadable] [unreadable] [unreadable] [unreadable]..
  24. GENERATING ANTIGENIC PEPTIDE/MHC BY CRYPTIC TRANSLATION
    Nilabh Shastri; Fiscal Year: 2010
    ....
  25. Brain Development on Adults with Schizophrenia
    George Bartzokis; Fiscal Year: 2008
    ..This will change our concept of how we could treat this illness, the feasibility of changing its lifelong course, and would encourage the development of novel pharmacologic interventions to improve myelination. [unreadable] [unreadable]..
  26. ASSEMBLY AND TRAFFICKING OF MHC CLASS II MOLECULES
    Hidde Ploegh; Fiscal Year: 2008
    ..H2 H4 mouse (autoimmune thyroiditis). We have backcrossed the CatB, CatL and CatS -/- mutations onto the NOD background and will explore the consequences of these cathepsin deficiencies for onset and severity of disease. ..
  27. Modulation of type I diabetes with NKT cells
    Luc Van Kaer; Fiscal Year: 2006
    ..These studies will provide a better understanding of the immunological mechanisms that result in autoimmunity, and may lead to the development of novel agents for treatment of type I diabetes and other autoimmune diseases. ..
  28. EXPRESSION, SPECIFICITY, AND FUNCTION OF LY49 FAMILY
    Wayne Yokoyama; Fiscal Year: 2001
    ..Thus, these studies will provide fundamental new information that will further elucidate the function of NK cells and their tolerance mechanisms. ..
  29. NOTCH SIGNALING IN THYMOCYTE DEVELOPMENT
    Michael Bevan; Fiscal Year: 2003
    ..It is hoped that the work will provide a better understanding of the integration of signals from the TCR, the glucocorticoid receptor, and Notch that developing T cells receive. ..
  30. CD8+ T CELL RECOGNITION OF TH1 AND TH2
    Hong Jiang; Fiscal Year: 2003
    ..We will determine if this difference uniquely applies to the recognition of TCR peptide presented by Qa-1 or if CD8+ T cells specific for other peptides presented by MHC class I molecules also distinguish between TH1 and TH2 targets. ..
  31. CELLULAR PATHWAYS OF OCULAR IMMUNOREGULATION
    ROBERT CONE; Fiscal Year: 2003
    ..Understanding of this axis could impact on the management o f inflammatory eye disease, organ transplants (e.g. cornea), ocular tumors and autoimmune disease. ..
  32. PHD PROGRAM IN IMMUNOLOGY
    Hidde Ploegh; Fiscal Year: 2004
    ..The experimental component usually requires 3-4 years to complete a body of work considered adequate for a written thesis. ..
  33. Linking Innate with Adaptive Immune Response
    Wayne Yokoyama; Fiscal Year: 2003
    ..This meeting will be especially rewarding for students and postdoctoral fellows in search of opportunities for future research and challenges. ..
  34. CELL BIOLOGY OF HEAT SHOCK PROTEIN MEDIATED IMMUNIZATION
    Hidde Ploegh; Fiscal Year: 2002
    ....
  35. HLA-G AND EQUIVALENT AND FETO-MATERNAL INTERACTION
    Hidde Ploegh; Fiscal Year: 2003
    ....
  36. BIOLOGY OF HUMAN UTERINE NK CELLS
    Ashley Moffett; Fiscal Year: 2004
    ..It could lead to novel therapeutic approaches in a wide range of disorders including infertility, miscarriage, disorders due to defective placentation (pre-eclampsia and IUGR) and menstrual disorders. ..
  37. Modulation of EAE with ligand-activated NKT cells
    Luc Van Kaer; Fiscal Year: 2005
    ..These reagents will permit the selective activation of distinct adaptive immune responses in vivo, which could be exploited for therapeutic intervention in MS and other human autoimmune diseases. ..
  38. ASSEMBLY OF MHC CLASS I MOLECULES IN VITRO AND IN VIVO
    Hidde Ploegh; Fiscal Year: 2007
    ..abstract_text> ..
  39. Immune Correlates of Protection in Drug-Resistant HIV
    Brinda Emu; Fiscal Year: 2008
    ..For Aims 1 and 2, I will use samples collected in an established cohort study. For Aim 3, I will conduct a prospective interventional study, where I will design and implement an independent clinical research project. ..
  40. Bioinformatic Mapping of HIV-1 Nef Manipulation of T-Cell Activation and Function
    Jason Barbour; Fiscal Year: 2008
    ..Variation in circulating strains of HIV-1 may account for this variation. We intend to map viral genetic determinants of T cell activation within the HIV-1 Nef protein. [unreadable] [unreadable] [unreadable]..
  41. Signaling Pathways in Hepatic Fibrogenesis
    Bruce Bacon; Fiscal Year: 2005
    ..Since activated HSC play a key role in hepatic fibrogenesis, these experiments will contribute to an improved understanding of the basic biochemical processes underlying hepatic fibrosis. ..
  42. Pulmonary Hypertension and the Hypoxic Response in SCD
    Victor Gordeuk; Fiscal Year: 2008
    ..Aim 3. Using micro array analysis and high throughput genotyping, examine patterns of gene expression and candidate gene polymorphisms of the HIF-mediated hypoxic response in SCD and CP patients with and without PHTN. ..
  43. Epidemiology and Incidence of Barrett's Esophagus
    DOUGLAS ALLEN CORLEY; Fiscal Year: 2010
    ..The proposed study explores how hormones associated with body fat may change the way the body heals after an injury, and increase the risk of cells developing precancerous changes. ..
  44. FORMATION AND SURVIVAL OF RED BLOOD CELLS
    Ernest Beutler; Fiscal Year: 2001
    ..Should these point mutations fail to alter gene transcription, a search will be made for other potential mutations in linkage disequilibrium with the known -5,-8 and -24 polymorphisms, by sequencing upstream through the promotor. ..
  45. MODULATION OF REGULATORY TOLERANCE TO TRANSPLANTS
    Christian LeGuern; Fiscal Year: 2009
    ..It is hoped that these studies will provide the impetus for the design of new therapeutic molecules with clinical application in transplantation biology. ..
  46. Cannabinoid Receptor Dynamics in T Cell Activation
    NICHOLAS GASCOIGNE; Fiscal Year: 2002
    ..We will express fluorescent CB2 in APC, to see how expression is affected by drug exposure and by interaction with T cells. ..
  47. Identification of auto antigens in ovarian cancer
    Ramila Philip; Fiscal Year: 2006
    ..abstract_text> ..
  48. MODULATION OF T LYMPHOCYTE REGULATION
    Christian LeGuern; Fiscal Year: 2009
    ..abstract_text> ..
  49. Copper's Role in Brain LRP-mediated Abeta Efflux and Aging
    Rashid Deane; Fiscal Year: 2010
    ..These studies may provide new therapeutic insights on how to lower brain A[unreadable] by controlling its CNS barriers transport in Cu-potentiated neurodegenerative disorders. ..
  50. Sex-based Differences in the Immune Response
    Betty Diamond; Fiscal Year: 2005
    ..Finally, we will investigate the differences in B cell responsiveness to estrogen in BALB/c and C57Bl/6 mice to understand what underlies an estrogen mediated breakdown in humoral self- tolerance. ..
  51. An antigen induced model of SLE
    Betty Diamond; Fiscal Year: 2005
    ..We will determine if an enhanced T cell response alters the repertoire of activated B cells. These studies, in composite, will help us understand how autoreactive B cells can be activated in vivo by antigen exposure. ..
  52. Exploiting porcine cytomegalovirus stealth mechanisms
    MARK CREW; Fiscal Year: 2005
    ..The Phase I project will be deemed successful when we have identified specific genes from PCMV which impart stealth to pig cells in vitro when exposed to cells from the human immune system. ..
  53. SOLUBLE T CELL RECEPTOR STUDIES ON MHC RESTRICTION
    NICHOLAS GASCOIGNE; Fiscal Year: 2006
    ..TCR dimerization will be investigated in solution, using biophysical methods including FRET, analytical ultracentrifugation and BIAcore. ..
  54. Isolation and Characterization of a Ferritin Receptor
    James Connor; Fiscal Year: 2005
    ..This project will significantly alter our thinking on brain iron transport and open novel directions for research in oligodendrocyte biology and diagnositic and therapeutic strategies in demyelinating disorders ..
  55. Immune Parameters in a Steroid Sparing Clinical Trial
    Nancy Reinsmoen; Fiscal Year: 2005
    ..Thus, the overall study is designed to use immune parameters to identify recipients at low vs. high risk for poor graft outcome, thereby allowing for individualization of immunosuppression aimed at improving long-term graft outcome. ..
  56. A Rapid Method for HLA-typing by Haplotyping
    Johannes Dapprich; Fiscal Year: 2006
    ..It is a further goal of Phase II to demonstrate the direct compatibility of HSE with existing SNP-mapping information and to expand the automation of HSE to a 96-well platform. ..
  57. Ethanol Effects on Antigen Presentation in Liver Cells
    Natalia Osna; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  58. EIAV Control by High Avidity Rev-Specific CTL Clones
    ROBERT MEALEY; Fiscal Year: 2005
    ..The information obtained from the proposed studies should have implications for HIV-1 immunotherapy and vaccine design, where experiments of this type may be more difficult. ..
  59. FASEB Research Conference on: Autoimmunity
    Betty Diamond; Fiscal Year: 2004
    ..Many investigators consider it to be the premier meeting on autoimmunity. ..
  60. Iron as a Nutritional Modifier of Toxic Neuropathy in HIV/AIDS
    Asha Kallianpur; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  61. SEVERE MALARIAL ANEMIA AND ALTERED IMMUNE FUNCTION
    Victor Gordeuk; Fiscal Year: 2004
    ..The nutritional status, underlying parasitic infections, and genotypes and numbers of infecting P. falciparum strains will also be characterized. ..
  62. Peptides/MHC-I complexes and CD8+T cells
    Herman Eisen; Fiscal Year: 2004
    ..The overall goal is to help provide a platform to aid in the development of immunization strategies leading to increased yields of potent memory CD8 T cells. ..
  63. ALABAMA/ZAMBIA HIV VACCINE CLINICAL TRIALS UNIT (HVTU)
    Paul Goepfert; Fiscal Year: 2006
    ..Recently, the Alabama clinic enrolled 125 higher-risk gay men in <5 months in the first US phase III trial. Plans for utilizing these cohorts and others are described. ..
  64. Regulatory T cells in transplantation tolerance
    James Markmann; Fiscal Year: 2008
    ..Collectively, these studies will further our understanding of regulatory T cell function in vivo and help to define their potential for application in the clinical transplant arena. ..
  65. MECHANISMS FOR FORMATION OF CELL MEMBRANE DOMAINS
    Michael Edidin; Fiscal Year: 2002
    ..The PI proposes to test his model using cells in which the barriers to lateral mobility are defective, sph/sph, alpha-spectrin-deficient, erythroleukemia cells, and cells in which vesicle traffic from and to the surface is inhibited. ..
  66. Antibody Immunotherapy to a Pro-apoptotic Tumor Antigen
    Kenneth Rock; Fiscal Year: 2004
    ..In another set of experiments, we will test the effect of p40 on human tumors transplanted into immunodeficient mice. ..
  67. CTL-BASED VACCINES FOR THE AIDS VIRUS
    David Watkins; Fiscal Year: 2003
    ..John Altman will synthesize MHC class I tetramers for CTL quantitation and Deborah Fuller will immunize animals using the gene gun. ..
  68. MECHANISMS OF ENZYMIC AND HYDRIDE TRANSFERS
    Gregory Petsko; Fiscal Year: 2006
    ..abstract_text> ..