title: A novel mechanism for the immunomodulatory functions of class II MHC-derived peptides.
abstract: There is now extensive evidence that synthetic peptides corresponding to linear sequences of MHC molecules are effective immunoregulators, targeting the immune response at many different sites. It has been previously shown that peptides derived from a highly conserved region of MHC class II inhibit proliferation to autoantigen and to both the direct and indirect pathways of allorecognition. This study demonstrates that inhibition of lymphocyte proliferation by nonpolymorphic MHC class II peptides, specifically HLA-DQA1, is sequence-specific and that the inhibitory effect is mediated through the induction of apoptosis in antigen-presenting cells via a caspase-independent mechanism. In addition, T lymphocytes stimulated in the presence of HLA-DQA1 are rendered hyporesponsive to subsequent stimuli. Immunomodulation by HLA-DQA1 is effective in vivo because it prevents both the priming and the effector function of primed allogeneic T cells in a murine DTH model. These observations have important implications for the development of a novel therapy for immune-mediated diseases.
authors.affiliation: Renal Division, Mount Sinai School of Medicine, New York, New York 10029, USA. Barbara.Murphy@mssm.edu
authors.forename: Barbara
authors.initials: B
authors.lastname: Murphy
authors.forename: Joyce
authors.initials: J
authors.lastname: Yu
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Jiao
authors.forename: Marvin
authors.initials: M
authors.lastname: Lin
authors.forename: Tanuja
authors.initials: T
authors.lastname: Chitnis
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Sayegh
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology*; D059848:HLA-DQ alpha-Chains; D008297:Male; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology
chemical_list: D000276:Adjuvants, Immunologic; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen