Effect of single amino acid substitution at residue 167 of HLA-B51 on binding of antibodies and recognition of T cells.
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.
Department of Tumor Biology, University of Tokyo, Japan.
S
S
Nakayama
G
G
Kawaguchi
S
S
Karaki
T
T
Nagao
H
H
Uchida
K
K
Kashiwase
T
T
Akaza
T
T
Nasuno
M
M
Takiguchi
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D001666:Binding Sites, Antibody; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D015235:HLA-B Antigens / Q000737:chemistry* / Q000276:immunology*; D015797:HLA-B35 Antigen / Q000276:immunology; D059949:HLA-B51 Antigen; D006801:Humans; D007518:Isoantibodies / Q000276:immunology; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D000596:Amino Acids; D015235:HLA-B Antigens; D015797:HLA-B35 Antigen; D059949:HLA-B51 Antigen; D007518:Isoantibodies