REJECTION OF SKIN ALLOGRAFTS BY INDIRECT ALLORECOGNITION OF DONOR CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX PEPTIDES

LEW (RT1l) rats were immunized with peptides corresponding to the alpha-helical region of the alpha-1 domain (peptide 1), the beta-sheet of the alpha-2 domain (peptide 2), and the alpha-helical region of the alpha-2 domain (peptide 3) of the RT1-A(av1) classical class I molecule of the DA (RT1av1) strain. The immunizations were without carriers, and the objective was to prime to indirect allorecognition without influencing direct recognition of the RT1-A(av1) molecule. The LEW rats mounted strong primary and secondary antibody responses to peptides 1 and 3, but only weak secondary responses to peptide 2. None of the antipeptide antibodies crossreacted with intact RT1-A(av1) class I molecules. The immunizations also resulted in LEW antigen-presenting cell-dependent, CD4+ T cell proliferative responses, which were very strong against peptide 1 and weakest against peptide 2. LEW rats immunized with peptides 1 or 3, but most effectively with both peptides 1 and 3 together, showed accelerated rejection of DA skin allografts. This effect was not observed in LEW rats immunized with peptide 2. In response to the DA skin allograft, the peptide-immunized LEW rats showed markedly accelerated kinetics of antibody production to the intact RT1-A(av1) molecule. These data demonstrate that indirect allorecognition can play an important role in allograft rejection and have important implications for understanding allograft rejection and its regulation.