Induction of tolerance to minor histocompatibility antigens by synthetic peptides

Background. H-Y is a transplantation antigen that has provided a useful tool for exploring graft rejection in responses to minor histocompatibility antigens encoded by genes on the Y chromosome. Recently, two mouse Y chromosome genes, Uty and Smcy have been characterized. Sequence screening for the presence of allele-specific MHC class I binding motifs identified two peptides, WI and KL, with Db binding motifs. Materials and methods. We have analyzed the immune response induced by in vivo immunization with H-Y peptides administered subcutaneously in adjuvant or in soluble form. Results. Subcutaneous injection of H-Y peptides in IFA induces CD8 T cells displaying cytotoxic and IFN-? activities. Conversely, the continuous delivery of soluble H-Y peptides by mini-osmotic pumps causes inhibition of antigen-specific cytotoxic activity and IFN-? production, but primes regulatory CD8 T cells which suppress both in vivo and in vitro the response of CD8 effector T cells specific for a different H-Y peptide However, this requires that both peptides are present on the same antigen presenting cells, thus indicating that regulatory cells exert linked suppression. Conclusions. The efficacy of a single peptide to tolerize CD8+ T lymphocytes might be relevant to design peptide-based therapies to downregulate CTL activity in transplant immunology.