Polymorphism of human minor histocompatibility antigens: T cell recognition of human minor histocompatibility peptides presented by HLA-B35 subtype molecules.

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-B3503 molecules, whereas the three CTL-resistant cell lines carry HLA-B3502, B3507, and B3508 molecules. The cytotoxicity of the CTL clones for three CTL weakly sensitive cell lines was enhanced by stimulation of human mH peptides isolated from HLA-B3501 molecules purified from C1R-B3501 cells. Small amounts of human mH peptides were isolated from B3503 molecules purified from these three CTL weakly sensitive cell lines. Taken together, these results indicate that weak recognition by the CTL clones of three CTL weakly sensitive cell line results from a small amount of the human mH peptides presented by B3503 molecules. The CTL-resistant cell line carrying B3507 loaded with the human mH peptides was killed by four CTL clones, whereas the cell lines carrying B3502 or B3508 loaded with the peptides were not. The human mH peptides were not isolated from B3507 molecules purified from the cell lines expressing this subtype, whereas small amounts of the human mH peptides were isolated from B3502 and B3508 molecules purified from the cell lines expressing the subtypes. These results indicate that failure of the CTL recognition of the cell line carrying B3507 is due to a lack of human mH antigens in this cell line. The failure of the CTL recognition of the cell lines carrying B3502 and B3508 is not explained by only the amount of the human mH peptides binding to these B35 subtype molecules because the amount of the human mH peptides eluted from B3502 and B3508 molecules purified from the cell lines carrying these B35 subtypes is almost the same as that eluted from B3503 molecules purified from the cell lines carrying B*3503.(ABSTRACT TRUNCATED AT 400 WORDS)