ANALYSIS OF ALLOANTIGENIC PEPTIDES

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Incompatibility of human minor histocompatibility (hmH) antigens can induce rejection of grafts in organ transplantation and graft-versus-host reactions in bone marrow transplantation. In spite of their importance in clinical transplantation, hmH antigens are not well studied. Previous studies have demonstrated the expression of hmH antigens on T and B cells, hematopoietic progenitor cells and keratinocytes. We have for the first time demonstrated the expression of hmH antigens on cultured kidney cells using HLA-B35-restricted, hmH antigen-specific cytotoxic T lymphocyte (CTL) clones, which were previously established from a patient who rejected two kidneys from HLA-identical sisters.To investigate the polymorphism of human minor histocompatibility (mH) antigens, PBLs from 23 Japanese individuals and 25 German individuals with HLA-B35 were studied by using four human mH antigen-specific, HLA-B35-restricted CTL clones. The CTL clones killed PHA-stimulated PBLs from all 23 Japanese individuals. On the other hand, they killed the PHA-stimulated PBLs from 19 of 25 German individuals and partially killed the PHA-stimulated PBLs from three German individuals (CTL weakly sensitive cell line) ; those from another three individuals (CTL-resistant cell line) were not killed by the CTL clones. All of three CTL weakly sensitive cell lines carry HLA-B^*3503 molecules, whereas the three CTL-resistant cell lines carry HLA-B^*3502, B^*3507, and B^*3508 molecules. Thus, the presentation of minor H antigen was affected by the aminoacid substitutions of peptide binding groove in HLA class l morecules.