Effect of single amino acid substitution at residue 167 of HLA-B51 on binding of antibodies and recognition of T cells

• Published in: Human immunology Vol. 39; no. 3; p. 211
• Main Authors: Nakayama, S, Kawaguchi, G, Karaki, S, Nagao, T, Uchida, H, Kashiwase, K, Akaza, T, Nasuno, T, Takiguchi, M
• Format: Journal Article
• Language: English
• Published: United States 01-03-1994
• Subjects: Amino Acid Sequence; Amino Acids - chemistry; Binding Sites, Antibody; Cell Line; Cytotoxicity Tests, Immunologic; HLA-B Antigens - chemistry; HLA-B Antigens - immunology; HLA-B35 Antigen - immunology; HLA-B51 Antigen; Humans; Isoantibodies - immunology; Molecular Sequence Data; Structure-Activity Relationship; T-Lymphocytes, Cytotoxic - immunology; Transfection
• DOI: 10.1016/0198-8859(94)90262-3
• ISSN: 0198-8859

We recently showed that a single amino acid substitution of tryptophane into glycine at residue 167 facing the "A pocket" forms a novel HLA-B51 subtype, B*5103, which is serologically discriminated as HLA-BTA. CDC assay of human alloantisera specific for the HLA-B5 CREG against B*5103- or B*5101-transfected human B-cell line, Hmy2C1R (C1R), supported the belief that human alloantisera can discriminate B*5103 from B*5101 Ag. Moreover, we found that 4D12 anti-B5, B35 CREG mAb cannot bind to B*5103 Ag on C1R cells or L cells although it binds to B*5101 Ag on both cells. These results indicate that alloantibodies can detect a single amino acid substitution at residue 167. Furthermore, it was suggested that 4D12 mAb recognizes the structure formed by the HLA-peptide complex since this mAb did not bind to empty HLA-B5, B35 CREG Ag on RMA-S transfectants. Six of eight anti-HLA-B*5101 CTL clones are not able to kill C1R cells expressing B*5103, indicating that conformational change of the A pocket by substitution at residue 167 has a crucial influence on recognition of alloreactive T cells. Therefore, discrimination of B*5103 from B*5101 would seem to be important in bone marrow transplantation.