Research Topics
| Kenneth RockSummaryAffiliation: University of Massachusetts Medical School Country: USA Publications
Research Grants
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Publications
Innate and adaptive immune responses to cell deathKenneth L Rock
Department of Pathology, UMass Medical School, Worcester, MA 01655, USA
Immunol Rev 243:191-205. 2011..These pathways underlie the pathogenesis of a number of diseases...- Cross-presentation: underlying mechanisms and role in immune surveillanceKenneth L Rock
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
Immunol Rev 207:166-83. 2005..In addition to the critical role of cross-presentation in normal immune physiology, this pathway has considerable potential for being exploited for developing subunit vaccines that elicit both CD4(+) and CD8(+) T-cell immunity... - The inflammatory response to cell deathKenneth L Rock
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
Annu Rev Pathol 3:99-126. 2008..Here we review what is presently known about the sterile inflammatory response and its underlying mechanisms... - The sterile inflammatory responseKenneth L Rock
Department of Pathology, University of Massachusetts Medical School, Worcester, 01655, USA
Annu Rev Immunol 28:321-42. 2010..Here we review established and emerging data about these responses... - Proteases in MHC class I presentation and cross-presentationKenneth L Rock
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
J Immunol 184:9-15. 2010..The Ag presentation mechanisms used by the sentinel cells can be different from those in other cells. This article will review these mechanisms with a focus in each case on how antigenic peptides are generated for presentation... - Natural endogenous adjuvantsKenneth L Rock
Department of Pathology, UMass Medical School, Worcester, MA 01655, USA
Springer Semin Immunopathol 26:231-46. 2005..The potential biological roles of this class of adjuvants are discussed... - Analysis of the role of bleomycin hydrolase in antigen presentation and the generation of CD8 T cell responsesCharles F Towne
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
J Immunol 178:6923-30. 2007..Therefore, BH does influence presentation of some Ags, although its role is largely redundant with other aminopeptidases... - Characterizing the specificity and cooperation of aminopeptidases in the cytosol and endoplasmic reticulum during MHC class I antigen presentationArron Hearn
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
J Immunol 184:4725-32. 2010..Because N-terminal trimming has different specificity in the cytosol and ER, the cleavage of peptides in both of these compartments serves to broaden the repertoire of sequences that are presented... - The specificity of trimming of MHC class I-presented peptides in the endoplasmic reticulumArron Hearn
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
J Immunol 183:5526-36. 2009..These data define key determinants in the specificity of Ag processing... - Leucine aminopeptidase is not essential for trimming peptides in the cytosol or generating epitopes for MHC class I antigen presentationCharles F Towne
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
J Immunol 175:6605-14. 2005..These data demonstrate that LAP is not an essential enzyme for generating most MHC class I-presented peptides and reveal redundancy in the function of cellular aminopeptidases... - The cytosolic endopeptidase, thimet oligopeptidase, destroys antigenic peptides and limits the extent of MHC class I antigen presentationIan A York
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
Immunity 18:429-40. 2003..TOP therefore plays an important role in vivo in degrading peptides released by proteasomes and is a significant factor limiting the extent of antigen presentation... - Analysis of the role of tripeptidyl peptidase II in MHC class I antigen presentation in vivoMasahiro Kawahara
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
J Immunol 183:6069-77. 2009.... - Both dendritic cells and macrophages can stimulate naive CD8 T cells in vivo to proliferate, develop effector function, and differentiate into memory cellsLu-Ann M Pozzi
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
J Immunol 175:2071-81. 2005..Because Mphi can be very abundant cells, especially at sites of infection and inflammation, they have the potential to play an important role in immune surveillance and the initiation of T cell immunity... - Puromycin-sensitive aminopeptidase limits MHC class I presentation in dendritic cells but does not affect CD8 T cell responses during viral infectionsCharles F Towne
Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
J Immunol 180:1704-12. 2008.... - Identification of the cellular sensor that stimulates the inflammatory response to sterile cell deathHajime Kono
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
J Immunol 184:4470-8. 2010..One key way they accomplish this important task is by producing IL-1alpha that is needed to initiate the inflammatory response... - Cutting edge: elimination of an endogenous adjuvant reduces the activation of CD8 T lymphocytes to transplanted cells and in an autoimmune diabetes modelYan Shi
Department of Pathology, University of Massachusetts Medical School, Worcester, 01655, USA
J Immunol 176:3905-8. 2006..These findings support the concept that danger signals contribute to the T cell responses to cell-associated Ags by activating APCs and identify uric acid as one of these signals... - Cellular protein is the source of cross-priming antigen in vivoLianjun Shen
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
Proc Natl Acad Sci U S A 101:3035-40. 2004..Therefore, cellular proteins, rather than peptides or heat shock protein/peptide complexes, are the major source of antigen that is transferred from antigen-bearing cells and cross-presented in vivo... - CD40-CD40 ligand interaction between dendritic cells and CD8+ T cells is needed to stimulate maximal T cell responses in the absence of CD4+ T cell helpMaria Genevive H Hernandez
Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
J Immunol 178:2844-52. 2007..Altogether, these results reveal a direct and unique role for CD40L on CD8+ T cells interacting with CD40 on APCs that affects the magnitude and quality of CD8+ T cell responses... - How dying cells alert the immune system to dangerHajime Kono
Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA
Nat Rev Immunol 8:279-89. 2008..The importance of these processes to host defence and disease pathogenesis has only been appreciated relatively recently. This article reviews our current knowledge of these processes... - Uric acid promotes an acute inflammatory response to sterile cell death in miceHajime Kono
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
J Clin Invest 120:1939-49. 2010..Collectively, our data identify uric acid as a proinflammatory molecule released from dying cells that contributes significantly to the cell death-induced inflammatory responses in vivo... - Exiting the outside world for cross-presentationKenneth L Rock
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
Immunity 25:523-5. 2006.... - Molecular identification of a danger signal that alerts the immune system to dying cellsYan Shi
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
Nature 425:516-21. 2003..Our findings provide a molecular link between cell injury and immunity and have important implications for vaccines, autoimmunity and inflammation... - Tripeptidyl peptidase II is the major peptidase needed to trim long antigenic precursors, but is not required for most MHC class I antigen presentationIan A York
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
J Immunol 177:1434-43. 2006..Moreover, these findings reveal that three sequential proteolytic steps (by proteasomes, TPPII, and then ER aminopepsidase 1) are required for the generation of a subset of epitopes... - Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims MHC class I-presented peptides in vivo and plays an important role in immunodominanceIan A York
Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
Proc Natl Acad Sci U S A 103:9202-7. 2006..Moreover, peptide trimming and the resulting abundance of peptide-MHC complexes are dominant factors in establishing immunodominance... - Priming of T cells by exogenous antigen cross-presented on MHC class I moleculesLianjun Shen
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
Curr Opin Immunol 18:85-91. 2006..This pathway is of considerable interest because it has an important role in the immune surveillance of tissues for pathogens and cancers... - Post-proteasomal antigen processing for major histocompatibility complex class I presentationKenneth L Rock
Department of Pathology, University of Massachusetts Medical Center, Worcester, MA 01655, USA
Nat Immunol 5:670-7. 2004..Thus, the extent of antigen presentation depends on the balance between several proteolytic processes that may generate or destroy epitopes... - The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8-9 residuesIan A York
Department of Pathology, University of Massachusetts Medical Center, Worcester, MA 01655, USA
Nat Immunol 3:1177-84. 2002..However, after interferon-gamma treatment, which causes proteasomes to produce more NH2-extended antigenic precursors, ERAP1 increased the supply of peptides for MHC class I antigen presentation... - A mutant cell with a novel defect in MHC class I quality controlIan A York
Department of Pathology, University of Massachusetts Medical Center, Worcester, 01655, USA
J Immunol 174:6839-46. 2005..The 4S8.12 cells provide strong genetic evidence for a novel component in the MHC class I pathway. This as-yet unidentified gene is important in early assembly of primate, but not mouse, MHC class I complexes... - Cell death releases endogenous adjuvants that selectively enhance immune surveillance of particulate antigensYan Shi
Department of Pathology, University of Massachusetts Medical School, Worcester, USA
Eur J Immunol 32:155-62. 2002..This process will allow the immune system to rapidly detect and respond to viral infections and tumors... - CD40 on APCs is needed for optimal programming, maintenance, and recall of CD8+ T cell memory even in the absence of CD4+ T cell helpMaria Genevive H Hernandez
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
J Immunol 180:4382-90. 2008..Therefore, CD40 signaling on APCs plays an important role in all phases of a memory CD8(+) T cell response... - Protein degradation and the generation of MHC class I-presented peptidesKenneth L Rock
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
Adv Immunol 80:1-70. 2002.... - NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystalsPeter Duewell
Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Nature 464:1357-61. 2010..These findings provide new insights into the pathogenesis of atherosclerosis and indicate new potential molecular targets for the therapy of this disease... - MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystalsChun Jen Chen
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
J Clin Invest 116:2262-71. 2006..These results indicate that IL-1 is essential for the MSU-induced inflammatory response and that the requirement of MyD88 in this process is primarily through its function as an adaptor molecule in the IL-1R signaling pathway... - Identification of a key pathway required for the sterile inflammatory response triggered by dying cellsChun Jen Chen
Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Room S2 109, Worcester, Massachusetts 01655, USA
Nat Med 13:851-6. 2007.... - Important role of cathepsin S in generating peptides for TAP-independent MHC class I crosspresentation in vivoLianjun 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... - Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilizationVeit Hornung
Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Nat Immunol 9:847-56. 2008..Our results indicate that the NALP3 inflammasome senses lysosomal damage as an endogenous 'danger' signal... - The ins and outs of cross-presentationKenneth L Rock
Nat Immunol 4:941-3. 2003 - An IFN-gamma-induced aminopeptidase in the ER, ERAP1, trims precursors to MHC class I-presented peptidesTomo 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... - The importance of the proteasome and subsequent proteolytic steps in the generation of antigenic peptidesAlfred L Goldberg
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
Mol Immunol 39:147-64. 2002..If cells express large amounts of TOP, class I presentation decreases, and if TOP is inhibited, presentation increases. Thus, peptide degradation in the cytosol appears to limit the efficiency of antigen presentation... - Pillars article: Antigen presentation by hapten-specific B lymphocytes. I. Role of surface immunoglobulin receptors. 1984Kenneth L Rock
J Immunol 179:7194-205. 2007 - Characterization of a proapoptotic antiganglioside GM2 monoclonal antibody and evaluation of its therapeutic effect on melanoma and small cell lung carcinoma xenograftsMarc W Retter
Antigen Discovery and Preclinical Biology, Corixa Corporation, Seattle, Washington, USA
Cancer Res 65:6425-34. 2005..Therefore, monoclonal antibody DMF10.167.4 has immunotherapeutic potential...
Research Grants
- Immunobiology of Antigen Presenting Cells in VivoKenneth Rock; Fiscal Year: 2006..The goals of this Aim are to test these hypotheses and determine the underlying mechanism for the loss APCs. ..
- IMMUNOBIOLOGY OF MHC RESTRICTION OF T CELLSKenneth Rock; Fiscal Year: 2007....
- IMMUNOBIOLOGY OF CTL RESPONSES TO EXOGENOUS ANTIGENSKenneth Rock; Fiscal Year: 2007..Our underlying hypothesis is that cell injury results in the release of MSU that then provides a danger signal, which stimulates immune responses to co-released autoantigens in genetically susceptible hosts. ..
- IMMUNOBIOLOGY OF MHC RESTRICTION OF T-CELLSKenneth Rock; Fiscal Year: 2009..The information gained by the proposed studies may lead to a better ability to predict and monitor immune responses to viruses and cancers and ultimately aid in the development of vaccines for these diseases. ..
- How cell death and sterile particulates stimulate inflammation and diseaseKenneth Rock; Fiscal Year: 2009..The information gained by the proposed studies may lead to new treatments to block the inflammatory response and thereby prevent or treat diseases. ..
- Immunobiology of CTL Responses to Exogenous AntigenKenneth Rock; Fiscal Year: 2009..The information gained by the proposed studies may lead to a better ability to predict and monitor immune responses to viruses and cancers and ultimately aid in the development of vaccines for these diseases. ..
- IMMUNOBIOLOGY OF MHC RESTRICTION OF T-CELLSKenneth L Rock; Fiscal Year: 2010..The information gained by the proposed studies may lead to a better ability to predict and monitor immune responses to viruses and cancers and ultimately aid in the development of vaccines for these diseases. ..
- How cell death and sterile particulates stimulate inflammation and diseaseKenneth L Rock; Fiscal Year: 2010..The information gained by the proposed studies may lead to new treatments to block the inflammatory response and thereby prevent or treat diseases. ..
- VACCINE STRATEGIES FOR IMMUNOTHERAPY OF CANCERKenneth Rock; Fiscal Year: 2002..In addition they will examine whether these manipulations lead to more effective immunotherapy due to stronger responses or by preventing tumors from evading immune responses. ..
- IMMUNOBIOLOGY OF CTL RESPONSES TO EXOGENOUS ANTIGENSKenneth Rock; Fiscal Year: 2003..g. cannot be infected with a virus) and when animals lack the exogenous pathway of presentation. We will also examine the importance of MHC class II presentation and costimulation in the generating responses in these settings. ..
- Antibody Immunotherapy to a Pro-apoptotic Tumor AntigenKenneth Rock; Fiscal Year: 2004..In another set of experiments, we will test the effect of p40 on human tumors transplanted into immunodeficient mice. ..
- Immunobiology of CTL Responses to Exogenous AntigenKenneth L Rock; Fiscal Year: 2010..The information gained by the proposed studies may lead to a better ability to predict and monitor immune responses to viruses and cancers and ultimately aid in the development of vaccines for these diseases. ..