Peptide-mediated immunosuppression.

Abstract

There is now a substantial body of data demonstrating the abilities of synthetic peptides and peptide analogues to inhibit the auto- and alloimmune response in vitro and in vivo. We have studied the immunomodulatory role of synthetic peptides derived from highly conserved regions of the class II MHC alpha chain. These MHC-derived peptides inhibit the rat, human, and mouse mixed lymphocyte response (MLR), proliferation to autoantigen, cytokine production, and cytolytic T lymphocyte (CTL) generation. Our studies demonstrated that the inhibitory effect of the MHC class II nonpolymorphic peptides is mediated through the induction of apoptosis in APCs via a nonclassic caspase-independent pathway. In addition, T lymphocytes initially stimulated in the presence of HLA-DQA1 are rendered hyporesponsive to subsequent stimuli. Immunomodulation by HLA-DQA1 was effective in vivo because it prevented both the priming and the effector function of primed allogeneic T cells in a murine DTH model. Our data demonstrate that peptides derived from highly conserved regions of the class II MHC alpha chain can alter T-lymphocyte immune responses both in vitro and in vivo. These results have important implications for the development of a novel therapy for immune mediated diseases.