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-Aav1 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-Aav1 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-Aav1 class I molecules. The immunization 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-Aav1 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.
Fangmann
J
J
Division of Cell and Molecular Biology, Institute of Child Health, London, United Kingdom.
Dalchau
R
R
Fabre
J W
JW
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D004261:DNA Replication; D006084:Graft Rejection; D015789:HLA-A2 Antigen / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007518:Isoantibodies / Q000276:immunology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology* / Q000494:pharmacology; D011487:Protein Conformation; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D016038:Skin Transplantation / Q000276:immunology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
D000911:Antibodies, Monoclonal; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D007518:Isoantibodies; D010455:Peptides