Research Topics
Genomes and Genes
| Marcus AltfeldSummaryAffiliation: Massachusetts General Hospital Country: USA Publications
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Publications
Human immunodeficiency virus type 1 specific cytotoxic T lymphocyte responses in Chinese infected with HIV-1 B'/C Recombinant (CRF07_BC)Jianping Chen
State Key Laboratory for Infectious Disease Control and Prevention, National Center for AIDS STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China
Retrovirology 4:62. 2007....
Standardization of cytokine flow cytometry assaysHolden T Maecker
BD Biosciences, San Jose, USA
BMC Immunol 6:13. 2005....
DCs and NK cells: critical effectors in the immune response to HIV-1Marcus Altfeld
Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
Nat Rev Immunol 11:176-86. 2011..The importance of understanding DC and NK cell crosstalk during HIV infection for the development of effective antiviral strategies is also discussed...
Hitting HIV where it hurts: an alternative approach to HIV vaccine designMarcus Altfeld
Partners AIDS Research Center, Infectious Disease Unit, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, MA 02129, USA
Trends Immunol 27:504-10. 2006....
The majority of currently circulating human immunodeficiency virus type 1 clade B viruses fail to prime cytotoxic T-lymphocyte responses against an otherwise immunodominant HLA-A2-restricted epitope: implications for vaccine designMarcus Altfeld
Partners AIDS Research Center, Massachusetts General Hospital, 149 13th St, Boston, MA 02129, USA
J Virol 79:5000-5. 2005....
The role of CD4(+) T helper cells in the cytotoxic T lymphocyte response to HIV-1M Altfeld
Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA
Curr Opin Immunol 12:375-80. 2000....
T(H)1 to T(H)2 shift of cytokines in peripheral blood of HIV-infected patients is detectable by reverse transcriptase polymerase chain reaction but not by enzyme-linked immunosorbent assay under nonstimulated conditionsM Altfeld
Department of Internal Medicine I, University of Bonn, Germany
J Acquir Immune Defic Syndr 23:287-94. 2000..Therefore, we determined tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-4, IL-10, and interferon-gamma (IFN-gamma) mRNA and serum levels in HIV-infected patients under nonstimulated conditions...
Selective escape from CD8+ T-cell responses represents a major driving force of human immunodeficiency virus type 1 (HIV-1) sequence diversity and reveals constraints on HIV-1 evolutionTodd M Allen
Howard Hughes Medical Institute, Partners AIDS Research Center, and Infectious Disease Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
J Virol 79:13239-49. 2005..The stereotypic nature of acquired mutations provides support for biochemical constraints limiting HIV-1 evolution and for the impact of CD8 escape mutations on viral fitness...
Selection, transmission, and reversion of an antigen-processing cytotoxic T-lymphocyte escape mutation in human immunodeficiency virus type 1 infectionTodd M Allen
Howard Hughes Medical Institute, Partners AIDS Research Center, Infectious Disease Division, Massachusetts General Hospital, and Division of AIDS, Harvard Medical School, Boston, MA, USA
J Virol 78:7069-78. 2004..Moreover, reversion of these mutations in the absence of the original immune pressure reveals the potential plasticity of immunologically selected evolutionary changes...
Control of human immunodeficiency virus replication by cytotoxic T lymphocytes targeting subdominant epitopesNicole Frahm
Partners AIDS Research Center, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115, USA
Nat Immunol 7:173-8. 2006..These data suggest that subdominant responses can contribute to in vivo viral control and that high HLA allele frequencies may drive the elimination of subdominant yet effective epitopes from circulating viral populations...
T cell receptor cross-recognition of an HIV-1 CD8+ T cell epitope presented by closely related alleles from the HLA-A3 superfamilyMathias Lichterfeld
Partners AIDS Research Center, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, MA, USA
Int Immunol 18:1179-88. 2006..Thus, despite distinct TCR recognition of HLA-A3 or HLA-A11 presented HIV-1 peptides in the vast majority of cases, specific TCRs can cross-recognize their antigen in the context of both HLA-A3 and HLA-A11...
The major genetic determinants of HIV-1 control affect HLA class I peptide presentationFlorencia Pereyra
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology MIT and Harvard, Boston, MA, USA
Science 330:1551-7. 2010..These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection...
Immune-driven recombination and loss of control after HIV superinfectionHendrik Streeck
Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
J Exp Med 205:1789-96. 2008..These data also support a role for cellular immune pressures in driving the selection of new recombinant forms of HIV...
Effects of thymic selection of the T-cell repertoire on HLA class I-associated control of HIV infectionAndrej Kosmrlj
Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts 02114, USA
Nature 465:350-4. 2010..Our results provide a conceptual framework that unifies diverse empirical observations, and have implications for vaccination strategies...
Single-stranded RNA derived from HIV-1 serves as a potent activator of NK cellsGalit Alter
Partners AIDS Research Center, Infectious Disease Unit, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, MA 02129, USA
J Immunol 178:7658-66. 2007....
Antigen load and viral sequence diversification determine the functional profile of HIV-1-specific CD8+ T cellsHendrik Streeck
Partners AIDS Research Center, Infectious Disease Unit, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts, United States of America
PLoS Med 5:e100. 2008....
Ligand-independent exhaustion of killer immunoglobulin-like receptor-positive CD8+ T cells in human immunodeficiency virus type 1 infectionGalit Alter
Partners AIDS Research Center, Massachusetts General Hospital, 149 13th Street, Boston, MA 02129, USA
J Virol 82:9668-77. 2008....
Comprehensive analysis of human immunodeficiency virus type 1-specific CD4 responses reveals marked immunodominance of gag and nef and the presence of broadly recognized peptidesDaniel E Kaufmann
Partners AIDS Research Center and Infectious Disease Unit, Howard Hughes Medical Institute, Massachusetts General Hospital, and Division of AIDS, Boston, Massachusetts 02114, USA
J Virol 78:4463-77. 2004..These findings have implications for the design of immunotherapeutic strategies and for testing candidate HIV vaccines...
De novo generation of escape variant-specific CD8+ T-cell responses following cytotoxic T-lymphocyte escape in chronic human immunodeficiency virus type 1 infectionTodd M Allen
Partners AIDS Research Center, Massachusetts General Hospital, Boston, 02129, USA
J Virol 79:12952-60. 2005....
Differential regulation of toll-like receptor pathways in acute and chronic HIV-1 infectionJ Judy Chang
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute Technology and Harvard, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
AIDS 26:533-41. 2012..Studies assessing the consequences of HIV-1 infection on the ability of innate immune cells to respond to TLR stimulation have come to varying conclusions...
Immunological and virological impact of highly active antiretroviral therapy initiated during acute HIV-1 infectionHendrik Streeck
Partners AIDS Research Center, Infectious Disease Unit, Massachusetts General Hospital, Charlestown, MA, 02129, USA
J Infect Dis 194:734-9. 2006..However, despite these immunological changes, no differences in viremia or in the CD4+ T cell count were found 6 months after HAART was stopped, when treated subjects were compared with untreated subjects...
Influence of HLA-B57 on clinical presentation and viral control during acute HIV-1 infectionMarcus Altfeld
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital, Boston, Massachusetts, USA
AIDS 17:2581-91. 2003..CONCLUSION: These data demonstrate that host genetic factors can influence the clinical manifestations of acute HIV-1 infection and provide a functional link between HLA-B57 and viral immune control...
Sequential deregulation of NK cell subset distribution and function starting in acute HIV-1 infectionGalit Alter
Partners AIDS Research Center, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, USA
Blood 106:3366-9. 2005..Taken together, these studies demonstrate a sequential impairment of NK cell function with persistent viral replication resulting from a progressive deregulation of NK cell subsets with distinct functional properties...
Upregulation of PD-L1 on monocytes and dendritic cells by HIV-1 derived TLR ligandsAngela Meier
Partners AIDS Research Center, Massachusetts General Hospital, Division of AIDS, Harvard Medical School, Boston, Massachusetts, USA
AIDS 22:655-8. 2008..These data suggest a mechanism through which HIV-1-derived TLR ligands might contribute to the functional impairment of virus-specific PD-1-positive T cells by inducing the upregulation of PD-L1 on antigen-presenting cells...
MyD88-dependent immune activation mediated by human immunodeficiency virus type 1-encoded Toll-like receptor ligandsAngela Meier
Partners AIDS Research Center, Massachusetts General Hospital, 149 13th Street, Boston, MA 02129, USA
J Virol 81:8180-91. 2007..These data provide an initial rationale for inhibiting the TLR pathway to directly reduce the chronic immune activation induced by HIV-1 and the associated immune pathogenesis...
Loss of HIV-1-specific CD8+ T cell proliferation after acute HIV-1 infection and restoration by vaccine-induced HIV-1-specific CD4+ T cellsMathias Lichterfeld
Partners AIDS Research Center, Massachusetts General Hospital, 149 13th St, Boston, MA 02129, USA
J Exp Med 200:701-12. 2004..This identification of a reversible defect in cell-mediated immunity in chronic HIV-1 infection has important implications for immunotherapeutic interventions...
Differences in the expressed HLA class I alleles effect the differential clustering of HIV type 1-specific T cell responses in infected Chinese and caucasiansXu G Yu
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts 02129, USA
AIDS Res Hum Retroviruses 20:557-64. 2004....
HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virusMarcus Altfeld
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts 02129, USA
Nature 420:434-9. 2002..The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development...
Selective depletion of high-avidity human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells after early HIV-1 infectionMathias Lichterfeld
Partners AIDS Research Center, Massachusetts General Hospital, and Division of AIDS, Harvard Medical School, Boston, MA 02129, USA
J Virol 81:4199-214. 2007..These data suggest that high-avidity HIV-1-specific CD8+ T-cell clones are recruited during early infection but are subsequently lost in the presence of persistent high-level viral replication...
Mutually exclusive T-cell receptor induction and differential susceptibility to human immunodeficiency virus type 1 mutational escape associated with a two-amino-acid difference between HLA class I subtypesXu G Yu
Partners AIDS Research Center, Massachusetts General Hospital, 149 13th Street, Room 5212, Charlestown, MA 02129, USA
J Virol 81:1619-31. 2007..These data show the influence of HLA allele subtypes on TCR selection and indicate that extensive TCR diversity is not a prerequisite to prevention of allowable viral mutations...
MHC class I chain-related protein A shedding in chronic HIV-1 infection is associated with profound NK cell dysfunctionAnne Nolting
Ragon Institute of Massachusetts General Hospital, Harvard University, Boston, MA, USA
Virology 406:12-20. 2010..Thus, like tumors, HIV-1 may indirectly suppress NK cell recognition of HIV-1-infected CD4+ T cells by enhancing NKG2D-ligand secretion into the serum resulting in a profound impairment of NK cell function...
Limited durability of viral control following treated acute HIV infectionDaniel E Kaufmann
Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
PLoS Med 1:e36. 2004..These data may be relevant to current efforts to develop an HIV-1 vaccine designed to retard disease progression rather than prevent infection since they indicate that durable maintenance of low-level viremia may be difficult to achieve...
Immune selection for altered antigen processing leads to cytotoxic T lymphocyte escape in chronic HIV-1 infectionRika Draenert
Howard Hughes Medical Institute, Charlestown, MA 02129, USA
J Exp Med 199:905-15. 2004..These results demonstrate that allele-associated sequence variation within the flanking region of CTL epitopes can alter antigen processing. Identifying such mutations is of major relevance in the construction of vaccine sequences...
Evolution of innate and adaptive effector cell functions during acute HIV-1 infectionGalit Alter
Partners AIDS Research Center, Infectious Disease Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
J Infect Dis 195:1452-60. 2007....
HIV-1 specific CD8+ T cells with an effector phenotype and control of viral replicationChristoph Hess
Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Harvard Medical School, Massachusetts, USA
Lancet 363:863-6. 2004..Our data show that full maturation of virus-specific CD8+ T cells is possible in the context of HIV-1-infection, and suggest that such maturation might be important in viral control...
HIV-1 Nef is preferentially recognized by CD8 T cells in primary HIV-1 infection despite a relatively high degree of genetic diversityMathias Lichterfeld
Partners AIDS Research Center and Howard Hughes Medical Institute, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts 02129, USA
AIDS 18:1383-92. 2004..Later diversification of responses to other proteins during prolonged antigen exposure provides evidence of the initial preferential immunogenicity of Nef epitopes compared to similarly conserved regions within other viral proteins...
A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cellsMathias Lichterfeld
Partners AIDS Research Center, Massachusetts General Hospital, and Harvard University Center for AIDS Research, Boston, MA 02129, USA
J Exp Med 204:2813-24. 2007....
Comparison of overlapping peptide sets for detection of antiviral CD8 and CD4 T cell responsesRika Draenert
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, MA 02129, USA
J Immunol Methods 275:19-29. 2003..We conclude that peptides ranging from 15 to 20 amino acids yield similar results in IFN-gamma-based Elispot and ICS assays, and that all are likely to underestimate the true breadth of responses to a given reference strain of virus...
HLA-B63 presents HLA-B57/B58-restricted cytotoxic T-lymphocyte epitopes and is associated with low human immunodeficiency virus loadNicole Frahm
Partners AIDS Research Center, Massachusetts General Hospital, No. 5214, 149 13th Street, Charlestown, MA 02129, USA
J Virol 79:10218-25. 2005..The data support an important role of the presented epitope in mediating relative control of HIV replication and help to better define immune correlates of controlled HIV infection...
HLA-Cw*0102-restricted HIV-1 p24 epitope variants can modulate the binding of the inhibitory KIR2DL2 receptor and primary NK cell functionLena Fadda
Ragon Institute of MGH, MIT and Harvard, Charlestown, Massachusetts, United States of America
PLoS Pathog 8:e1002805. 2012....
Preserved function of regulatory T cells in chronic HIV-1 infection despite decreased numbers in blood and tissueMathieu Angin
Ragon Institute of MGH, MIT and Harvard, Charlestown, MA 02129 2000, USA
J Infect Dis 205:1495-500. 2012..Despite quantitative changes in Tregs, HIV-1 infection was not associated with an impairment of ex vivo suppressive function of flow-sorted Tregs in both HIV controllers and untreated chronic progressors...
Induction of strong HIV-1-specific CD4+ T-cell responses using an HIV-1 gp120/NefTat vaccine adjuvanted with AS02A in antiretroviral-treated HIV-1-infected individualsMathias Lichterfeld
Ragon Institute of Massachusetts General Hospital, Boston, USA
J Acquir Immune Defic Syndr 59:1-9. 2012..Induction of HIV-1-specific CD4(+) T-cell responses by therapeutic vaccination represents an attractive intervention to potentially increase immune control of HIV-1...
Recognition of a defined region within p24 gag by CD8+ T cells during primary human immunodeficiency virus type 1 infection in individuals expressing protective HLA class I allelesHendrik Streeck
Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
J Virol 81:7725-31. 2007....
Enhanced detection of human immunodeficiency virus type 1-specific T-cell responses to highly variable regions by using peptides based on autologous virus sequencesMarcus Altfeld
Partners AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, and Division of AIDS, Harvard Medical School, Boston, Massachusetts, USA
J Virol 77:7330-40. 2003..They also demonstrate that CD8 T-cell responses to the variable HIV-1 proteins are more common than previously reported...
High degree of inter-clade cross-reactivity of HIV-1-specific T cell responses at the single peptide levelXu G Yu
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital, 149 13th Street, Boston, MA 02129, USA
AIDS 19:1449-56. 2005....
Marked epitope- and allele-specific differences in rates of mutation in human immunodeficiency type 1 (HIV-1) Gag, Pol, and Nef cytotoxic T-lymphocyte epitopes in acute/early HIV-1 infectionZabrina L Brumme
Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
J Virol 82:9216-27. 2008..Dramatic differences in escape and reversion rates across codons, genes, and HLA restrictions are observed, highlighting the complexity of viral adaptation to the host immune response...
Epithelial adhesion molecules can inhibit HIV-1-specific CD8⁺ T-cell functionsHendrik Streeck
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Blood 117:5112-22. 2011....
HIV-1 viral escape in infancy followed by emergence of a variant-specific CTL responseMargaret E Feeney
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
J Immunol 174:7524-30. 2005..Taken together, these findings indicate that the developing immune system of children may exhibit greater plasticity in responding to a continually evolving chronic viral infection...
HIV-1 adaptation to NK-cell-mediated immune pressureGalit Alter
Ragon Institute at MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA
Nature 476:96-100. 2011..NK cells might therefore have a previously underappreciated role in contributing to viral evolution...
HIV-1 Vpu represents a minor target for cytotoxic T lymphocytes in HIV-1-infectionMarylyn M Addo
Partners AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, MA 02114, USA
AIDS 16:1071-3. 2002..The epitope was shown to be highly conserved among HIV clade B sequences and is restricted by HLA-A*3303, an HLA allele commonly seen in Asian and west-African populations...
Common HIV-1 peptide variants mediate differential binding of KIR3DL1 to HLA-Bw4 moleculesLena Fadda
Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Bldg 149, 13th Street, Charlestown, MA 02129, USA
J Virol 85:5970-4. 2011....
Increased natural killer cell activity in viremic HIV-1 infectionGalit Alter
Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston 02129, USA
J Immunol 173:5305-11. 2004..Taken together, these data demonstrate that viremic HIV-1 infection is associated with a reduction in NK cell numbers and a perturbation of NK cell subsets, but increased overall NK cell activity...
Differential natural killer cell-mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypesGalit Alter
Partners AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, MA 02129, USA
J Exp Med 204:3027-36. 2007..These data provide the first functional evidence that variation at the KIR locus influences the effectiveness of NK cell activity in the containment of viral replication...
Early viral replication in lymph nodes provides HIV with a means by which to escape NK-cell-mediated controlRutger Luteijn
Ragon Institute of MGH, MIT and Harvard, Boston, MA 02129, USA
Eur J Immunol 41:2729-40. 2011....
Reduced frequencies of NKp30+NKp46+, CD161+, and NKG2D+ NK cells in acute HCV infection may predict viral clearanceGalit Alter
Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA
J Hepatol 55:278-88. 2011..Epidemiologic data support a role for particular NK cell receptor bearing populations in this control, yet the mechanism by which NK cells respond to HCV early in infection is unknown...
HIV-1-specific cytotoxicity is preferentially mediated by a subset of CD8(+) T cells producing both interferon-gamma and tumor necrosis factor-alphaMathias Lichterfeld
Partners AIDS Research Center, Massachusetts General Hospital, 149 13th St, Rm 6613, Boston, MA 02129, USA
Blood 104:487-94. 2004..These results suggest that HIV-1-specific cytotoxicity of CD8(+) T cells is preferentially mediated by a subset of CD8(+) T cells secreting both interferon-gamma and TNF-alpha...
Human immunodeficiency virus type 1-specific CD8+ T-cell responses during primary infection are major determinants of the viral set point and loss of CD4+ T cellsHendrik Streeck
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA
J Virol 83:7641-8. 2009..Taken together, these data show that the specificity of the initial CTL response to HIV is critical for the subsequent control of viremia and have important implications for the rational selection of antigens for future HIV-1 vaccines...
Epidemiologically linked transmission of HIV-1 illustrates the impact of host genetics on virological outcomeHendrik Streeck
Partners AIDS Research Center, Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
AIDS 23:259-62. 2009..These data suggest that genetic factors play an important role in the outcome of HIV-1 infection despite early therapy...
Protective HLA class I alleles that restrict acute-phase CD8+ T-cell responses are associated with viral escape mutations located in highly conserved regions of human immunodeficiency virus type 1Yaoyu E Wang
Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, USA
J Virol 83:1845-55. 2009....
Consistent patterns in the development and immunodominance of human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T-cell responses following acute HIV-1 infectionXu G Yu
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
J Virol 76:8690-701. 2002..These studies have important implications for vaccine design and evaluation...
HLA class I subtype-dependent expansion of KIR3DS1+ and KIR3DL1+ NK cells during acute human immunodeficiency virus type 1 infectionGalit Alter
Ragon Institute of MGH, MIT, Boston, Massachusetts, USA
J Virol 83:6798-805. 2009..These data demonstrate for the first time the HLA class I subtype-dependent expansion of specific KIR(+) NK cells during an acute viral infection in humans...
Coordinate linkage of HIV evolution reveals regions of immunological vulnerabilityVincent Dahirel
Ragon Institute of Massachusetts General Hospital, and Harvard University, Boston, MA 02129, USA
Proc Natl Acad Sci U S A 108:11530-5. 2011..Targeting such regions with higher order evolutionary constraints provides a novel approach to immunogen design for a vaccine against HIV and other rapidly mutating viruses...
IL-10 induces aberrant deletion of dendritic cells by natural killer cells in the context of HIV infectionGalit Alter
Ragon Institute of MGH, MIT, and Harvard, Charlestown, Massachusetts 02129, USA
J Clin Invest 120:1905-13. 2010....
Alterations in natural killer cell receptor profiles during HIV type 1 disease progression among chronically infected South African adultsAmbrose H W Wong
Ragon Institute of MGH, MIT, and Harvard formerly Partners AIDS Research Center, Massachusetts General Hospital, Charleston, Massachusetts 02129, USA
AIDS Res Hum Retroviruses 26:459-69. 2010..These findings suggest that modulation of receptor expression on NK cells may play a role in HIV-1 pathogenesis, and provide new insights on immunological changes in advanced HIV-1 disease...
Immunodominance of HIV-1-specific CD8(+) T-cell responses in acute HIV-1 infection: at the crossroads of viral and host geneticsMathias Lichterfeld
Partners AIDS Research Center, Massachusetts General Hospital, Boston, MA 02129, USA
Trends Immunol 26:166-71. 2005....
Rapid loss of dendritic cell and monocyte responses to TLR ligands following venipunctureAngela Meier
Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
J Immunol Methods 339:132-40. 2008..Overnight shipment or extended rest of whole blood before processing therefore severely compromises the ability of APCs to respond to TLR ligands, and this has to be taken into consideration when designing multicenter trials...
Expansion of pre-existing, lymph node-localized CD8+ T cells during supervised treatment interruptions in chronic HIV-1 infectionMarcus Altfeld
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, MA 02129, USA
J Clin Invest 109:837-43. 2002..Furthermore, the enhanced CD8+ T cell responses observed during STI in chronically infected individuals is largely due to expansion of pre-existing virus-specific CD8+ T cells, rather than the induction of novel responses...
CD107a as a functional marker for the identification of natural killer cell activityGalit Alter
Partners AIDS Research Center, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Massachusetts, USA
J Immunol Methods 294:15-22. 2004..Cumulatively, the data presented here demonstrate that CD107a is a sensitive marker of NK cell activity...
IL-8 responsiveness defines a subset of CD8 T cells poised to killChristoph Hess
Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
Blood 104:3463-71. 2004..Thus, CXCR1 identifies a subset of CD8 T cells poised for immediate cytotoxicity and early recruitment into sites of innate immune system activation...
Rapid ex vivo isolation and long-term culture of human Th17 cellsHendrik Streeck
Partners AIDS Research Center, Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, United States
J Immunol Methods 333:115-25. 2008..In conclusion, this technique will allow for the first time the direct, ex vivo analysis of phenotypic and functional properties of Th17 cells...
Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1Angela Meier
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, Massachusetts, USA
Nat Med 15:955-9. 2009..Modulation of the TLR7 pathway in pDCs may therefore represent a new approach to reduce HIV-1-associated pathology...
Impact of intrapeptide epitope location on CD8 T cell recognition: implications for design of overlapping peptide panelsRika Draenert
Howard Hughes Medical Institute and Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School Division of AIDS, Boston, MA, USA
AIDS 18:871-6. 2004..CONCLUSION: When using overlapping peptides to screen for CD8 T cell responses, more sensitive detection will be achieved using known C-terminal anchor amino acid residues at the C-terminus...
Loss of HIV-1-specific T cell proliferation in chronic HIV-1 infection: cause or consequence of viral replication?Mathias Lichterfeld
Partners AIDS Research Center, Massachusetts General Hospital, Boston, Massachusetts 02129, USA
AIDS 19:1225-7. 2005
Low perforin and elevated SHIP-1 expression is associated with functional anergy of natural killer cells in chronic HIV-1 infectionGalit Alter
Partners AIDS Research Center, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts, USA
AIDS 20:1549-51. 2006..These CD3-CD56-CD16+ NK cells expressed SHIP-1 and had significantly reduced perforin levels. This observation suggests a mechanism for the reduced functional activity of CD3-CD56-CD16+ NK cells in chronic HIV-1 infection...
Functionally inert HIV-specific cytotoxic T lymphocytes do not play a major role in chronically infected adults and childrenP J Goulder
Partners AIDS Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
J Exp Med 192:1819-32. 2000..These data together show that functionally inert CTLs do not play a significant role in chronic pediatric or adult HIV infection...
Important contribution of p15 Gag-specific responses to the total Gag-specific CTL responsesXu G Yu
Partners AIDS Research Center, Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
AIDS 16:321-8. 2002....
Crippling HIV one mutation at a timeTodd M Allen
Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
J Exp Med 205:1003-7. 2008..These data suggest that targeting these and other conserved viral regions may be the key to developing an effective HIV-1 vaccine...
Rapid reversion of sequence polymorphisms dominates early human immunodeficiency virus type 1 evolutionBin Li
Partners AIDS Research Center, MGH East, CNY 6616, 149 13th Street, Charlestown, MA 02129, USA
J Virol 81:193-201. 2007....
HIV-1-specific interleukin-21+ CD4+ T cell responses contribute to durable viral control through the modulation of HIV-specific CD8+ T cell functionMathieu F Chevalier
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02129, USA
J Virol 85:733-41. 2011..These data suggest that HIV-1-specific IL-21(+) CD4(+) T cell responses might contribute to the control of viral replication in humans and are likely to be of great importance for vaccine design...
Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infectionM Altfeld
Partners AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA
J Exp Med 193:169-80. 2001..These data also provide rationale for therapeutic immunization aimed at broadening CTL responses in treated primary HIV infection...
NK cell function in HIV-1 infectionGalit Alter
Partners AIDS Research Center, Infectious Disease Unit, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, MA 02129, USA
Curr Mol Med 6:621-9. 2006..Here we present a review of the literature pertaining to both the effect of HIV-1 infection on NK cell activity and the potential role that this subset of cells may play in controlling HIV-1 disease...
Innate immune activation in primary HIV-1 infectionJ Judy Chang
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02129, USA
J Infect Dis 202:S297-301. 2010..Understanding the complexity of how innate responses affect the outcome of HIV-1 infection will help in the development of vaccines that can use innate immunity to enhance viral control with minimal pathogenesis...
HIV-1 superinfectionTodd M Allen
Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
J Allergy Clin Immunol 112:829-35; quiz 836. 2003..Herein we review the published reports of HIV-1 superinfection and highlight studies providing additional insight into the potential for HIV-1 superinfections to affect the global epidemic...
Parallel decrease in neurotoxin quinolinic acid and soluble tumor necrosis factor receptor p75 in serum during highly active antiretroviral therapy of HIV type 1 diseaseM P Look
Department of General Internal Medicine, University of Bonn, Germany
AIDS Res Hum Retroviruses 16:1215-21. 2000..This eventually led to a decrease in quinolinic acid formation. The parallel reduction of the immune activation marker sTNFR p75 supports this hypothesis...
Evolution and transmission of stable CTL escape mutations in HIV infectionP J Goulder
Partners AIDS Research Center, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts 02114, USA
Nature 412:334-8. 2001..These data suggest that CTL escape mutations in epitopes associated with suppression of viraemia will accumulate as the epidemic progresses, and therefore have important implications for vaccine design...
Vpr is preferentially targeted by CTL during HIV-1 infectionM Altfeld
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA
J Immunol 167:2743-52. 2001..These findings will be important in evaluating the specificity and breadth of immune responses during acute and chronic infection, and in the design and testing of candidate HIV vaccines...
Cytotoxic T-lymphocyte (CTL) responses directed against regulatory and accessory proteins in HIV-1 infectionM M Addo
Partners AIDS Research Center, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts, USA
DNA Cell Biol 21:671-8. 2002....
The HIV-1 regulatory proteins Tat and Rev are frequently targeted by cytotoxic T lymphocytes derived from HIV-1-infected individualsM M Addo
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Proc Natl Acad Sci U S A 98:1781-6. 2001..Despite the small size of these proteins, multiple CTL epitopes were identified in each. These data indicate that Tat and Rev are frequently targeted by CTL in natural HIV-1 infection and may be important targets for HIV vaccines...
NK cells in HIV-1 infection: evidence for their role in the control of HIV-1 infectionG Alter
Partners AIDS Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA
J Intern Med 265:29-42. 2009..In this review we highlight recent evidence that suggests that NK cells influence the clinical fate of HIV-infected individuals...
Regulatory and accessory HIV-1 proteins: potential targets for HIV-1 vaccines?X G Yu
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Curr Med Chem 12:741-7. 2005..A multi-component vaccine, with the inclusion of these proteins plus structural proteins remains the most promising choice for an effective AIDS vaccine...
Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral loadM M Addo
Partners AIDS Research Center, Massachusetts General Hospital and Harvard Medical School. Fenway Community Health Center. Lemuel Shattuck Hospital, Boston, Massachusetts 02129, USA
J Virol 77:2081-92. 2003....
Limited value of PCR for detection of Toxoplasma gondii in blood from human immunodeficiency virus-infected patientsC Franzen
Department of Internal Medicine I, University of Cologne, Germany
J Clin Microbiol 35:2639-41. 1997..The sensitivity was only 25%, but the specificity was very high (100%), so this technique may be useful for discriminating between cerebral toxoplasmosis and other brain diseases which may be mistaken for toxoplasmosis...
Rev activity determines sensitivity of HIV-1-infected primary T cells to CTL killingKevin R Bobbitt
Department of Internal Medicine, The University of Michigan, Ann Arbor, MI 48109, USA
Immunity 18:289-99. 2003..Thus, rev alleles with low activity may have a selective advantage in infected people with effective immune responses...
Viremia control despite escape from a rapid and potent autologous neutralizing antibody response after therapy cessation in an HIV-1-infected individualDavid C Montefiori
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
J Immunol 170:3906-14. 2003..We postulate that an early effective neutralizing Ab response can provide long-term clinical benefits despite neutralization escape...
Clustering patterns of cytotoxic T-lymphocyte epitopes in human immunodeficiency virus type 1 (HIV-1) proteins reveal imprints of immune evasion on HIV-1 global variationKarina Yusim
Los Alamos National Laboratory, Los Alamos, New Mexico 87545. Santa Fe Institute, Santa Fe, New Mexico 87501, USA
J Virol 76:8757-68. 2002....
Detection of KIR3DS1 on the cell surface of peripheral blood NK cells facilitates identification of a novel null allele and assessment of KIR3DS1 expression during HIV-1 infectionVeronique Pascal
Cancer and Inflammation Program, Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute Frederick, Frederick, MD 21702, USA
J Immunol 179:1625-33. 2007....
Availability of a diversely avid CD8+ T cell repertoire specific for the subdominant HLA-A2-restricted HIV-1 Gag p2419-27 epitopeKeri L Schaubert
Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA
J Immunol 178:7756-66. 2007....
Novel KIR3DL1 alleles and their expression levels on NK cells: convergent evolution of KIR3DL1 phenotype variation?Rasmi Thomas
Cancer and Inflammation Program, Laboratory of Experimental Immunology, National Cancer Institute, Frederick, MD 21702, USA
J Immunol 180:6743-50. 2008..These results raise the possibility that KIR3DL1 evolution maintains variation in KIR3DL1 cell-surface expression levels, potentially due to the effect of such variation on functional capacity...
HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8(+) T Cell Response against HIV-1Marcus Altfeld
PLoS Med 3:e403. 2006....
Relative dominance of Env-gp41-specific cytotoxic T lymphocytes responses in HIV-1 advanced infectionYan Zhuang
Department of Infectious Diseases, Tangdu Hospital Affiliated to the Fourth Military Medical University, PR China
Curr HIV Res 6:239-45. 2008....
PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progressionCheryl L Day
HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu Natal, Durban 4013, South Africa
Nature 443:350-4. 2006..Moreover, this pathway of reversible T-cell impairment provides a potential target for enhancing the function of exhausted T cells in chronic HIV infection...
Research Grants
- CD8+ T cell function in HIV-1 infectionMarcus Altfeld; Fiscal Year: 2010....
- NK Cell Function in HIV-1 InfectionMarcus Altfeld; Fiscal Year: 2010..Impact of the KIR/HLA compound genotype on NK cell function b. Impact of the peptides presented by HLA on KIR-mediated recognition by NK cells ..
- Modulation of HIV-1 specific T cell function by TLR ligandsMarcus Altfeld; Fiscal Year: 2007....
- CD8+ T cell function in HIV-1 infectionMarcus Altfeld; Fiscal Year: 2007....
- NK Cell Function in HIV-1 InfectionMarcus Altfeld; Fiscal Year: 2007..Analysis of the mechanisms that determine NK cell recognition of HIV-1 infected cells a. Impact of the KIR/HLA compound genotype on NK cell function b. Impact of the peptides presented by HLA on KIR-mediated recognition by NK cells. ..
- CTL Responses to Regulatory and Accessory HIV-1 ProteinsMarcus Altfeld; Fiscal Year: 2006....
- TLR-mediated gender differences in HIV-1 pathogenesisMarcus Altfeld; Fiscal Year: 2010....
