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

Abstract

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. The cytotoxicity of the CTL clones for three CTL weakly sensitive cell lines was enhanced by stimulation of human mH peptides isolated from HLA-B*3501 molecules purified from C1R-B*3501 cells. Small amounts of human mH peptides were isolated from B*3503 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 B*3503 molecules. The CTL- resistant cell line carrying B*3507 loaded with the human mH peptides was killed by four CTL clones, whereas the cell lines carrying B*3502 or B*3508 loaded with the peptides were not. The human mH peptides were not isolated from B*3507 molecules purified from the cell lines expressing this subtype, whereas small amounts of the human mH peptides were isolated from B*3502 and B*3508 molecules purified from the cell lines expressing the subtypes. These results indicate that failure of the CTL recognition of the cell line carrying B*3507 is due to a lack of human mH antigens in this cell line. The failure of the CTL recognition of the cell lines carrying B*3502 and B*3508 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 B*3502 and B*3508 molecules purified from the cell lines carrying these B35 subtypes is almost the same as that eluted from B*3503 molecules purified from the cell lines carrying B*3503.(ABSTRACT TRUNCATED AT 400 WORDS)

Novel HLA‐A and HLA‐B alleles in South American Indians

“…Residue 156 contributes to peptide binding specificity pockets D and E while residue 167 shapes pocket A. A*0219 was not detected by serology, the loss of the A2‐serological epitope may be the result of the substitutions at residues 142 and 145, since it has been described that replacements at these codons hinder the HLA‐A2‐A28 supertypic epitope ( 42).…”

Motif of HLA-B*3503 peptide ligands

“…This would explain the failure of peptide specific, HLA-B'3501 alloreactive T cells to recognize HLA-B*3503 target cells (Steinle et al 1993). A strongly reduced T-cell recognition of minor histocompatibility antigens has also been seen when presented by HLA-B*3503 instead of HLA-B*3501 molecules (Beck et al 1995).…”

Allelic heterogeneity of HLA‐B35 subtypes in different populations as assessed by DNA typing

“…Family segregation studies showed linkage of Cw4 with the following B35 alleles: HLA-B*3502 and HLA-B*3503 in the individual DL, an Argentinean woman with Spanish ancestors (6,8, Table 2), and B*3501 in two Argentineans with Italian ancestors. In five Mexican Mestizos with presumably new B35 alleles (Table 2), the B35,Cw4 extended haplotype was also deduced from family segregation analysis (Gorodez-able to distinguish B*3501 from B"3502, B*3503, B*3505, B*3507 and B*3508 (10,18,20,29). The presence in one population of several functional HLA class I alleles not distinguished by serology has clinical implications in bone marrow transplantation.…”