Two subtypes of HLA-B51 differing by substitution at position 171 of the ?2 helix

Abstract

Newly defined antigens of the B5, B35 cross-reacting group have been found in Japanese and North American Indians. Nucleotide sequencing of the alleles encoding the Japanese B5.35 antigen and the variant B5 antigen from the Piman Indians show them to be identical. This new allele, B*5102, differs from B*5101 by a single nucleotide substitution that changes residue 171 from histidine to tyrosine. Residue 171, which is part of the alpha 2 helix, is believed to contribute directly to peptide interaction in the A pocket of the binding groove and is either histidine or tyrosine in all HLA-A, B, C heavy chains. Tyrosine 171 is shared by B*5102, B*3501, B*3502, and B*5301 and must be responsible for the serological cross-reactivities of these molecules not shared with B*5101. Stimulation of lymphocytes from a B*5101 positive donor with B*5102 positive cells failed to generate cytotoxic T cells with specificity for the difference between these molecules. However, one out of five clones of cytotoxic T cells raised against B*5101 failed to lyse targets expressing B*5102. Substitution of histidine for tyrosine at residue 171 affected recognition of HLA-B35-restricted human minor histocompatibility antigen-specific T cell clones.

Identification of type-specific cytotoxic T lymphocyte responses to homologous viral proteins in laboratory workers accidentally infected with HIV-1.

“…Although the epitope fits the HLA-B51 motif featuring a COOH-terminal leucine and an alanine at position 2 as anchor residues, the representative clone SE10 lysed one B51-matched B-LCL but failed to lyse four other B51 ϩ B-LCL, possibly because of polymorphism of the B51 allele (46). The second Env epitope mapped from subject LWS was a type-specific epitope in gp120, (RVKEKYQHL, aa 2-10) described below.…”

Molecular analysis of HLA-B39 subtypes

“…For example, recently defined HLA-B51 subtypes, HLA-B*5102 and B'5103, were originally suggested by serology as HLA-B5.35 and HLA-BTA, respectively (Kawaguchi et al 1992;Takiguchi et al 1992). Although HLA subtypes usually differ by only a few amino acid substitutions, the difference plays a critical role in the rejection of transplanted bone marrow cells (Fleischhauer et al 1990).…”

A complete type patient with Behçet's disease associated with HLA‐B*5102

“…Therefore, the frequency of HLA-B*5102 in the B51-positive patient group is 1.9% which is almost equal to the frequency of HLA-B*5102 in the B51-positive normal group (2.0%) in a Japanese population. B*5102 differs from B*5101 by a single nucleotide substitution that changes amino acid residue at position 171 from histidine to tyrosine in the heavy chain of class I molecule (Kawaguchi et al 1992). This fact indicates that the amino acid at position 171 which forms a part of pocket A in the HLA groove (Matusmura et al 1992) is not concerned with the susceptibility to BD, and further supports that the amino acids commonly and specifically existing among B51-antigen group (B*5101-B*5104 alleles), 63-asparagine and 67phenylalanine, are responsible for the predispositon to Behcet's disease.…”