title: Binding of nonamer peptides to three HLA-B51 molecules which differ by a single amino acid substitution in the A-pocket.
abstract: The interaction between 9-mer peptides and HLA-B51 molecules was investigated by quantitative peptide binding assay using RMA-S cells expressing human beta2-microglobulin and HLA-B51 molecules. Of 147 chemically synthesized 9-mer peptides possessing two anchor residues corresponding to the motif of HLA-B*5101 binding self-peptides, 27 peptides bound to HLA-B*5101 molecules. Pro and Ala at position 2 as well as Ile at position 9 were confirmed to be main anchor residues, while Gly at position 2 as well as Val, Leu, and Met at position 9 were weak anchor residues for HLA-B*5101. The A-pocket is suspected to have a critical role in peptide binding to MHC class I molecules because this pocket corresponds to the N-terminus of peptides and has a strong hydrogen bond formed by conserved Tyr residues. Further analysis of peptide binding to HLA-B*5102 and B*5103 molecules showed that a single amino acid substitution of Tyr for His at residue 171(B*5102) and that of Gly for Trp at residue 167 (B*5103) has a minimum effect in HLA-B51-peptide binding. Since previous studies showed that some HLA-B51 alloreactive CTL clones failed to kill the cells expressing HLA-B*5102 or HLA-B*5103, these results imply that the structural change of the A-pocket among HLA-B51 subtypes causes a critical conformational change of the epitope for TCR recognition rather than influences the interaction between peptides and MHC class I molecules.
authors.affiliation: Department of Tumor Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minota-ku, Tokyo 108, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kikuchi
authors.forename: T
authors.initials: T
authors.lastname: Sakaguchi
authors.forename: K
authors.initials: K
authors.lastname: Miwa
authors.forename: Y
authors.initials: Y
authors.lastname: Takamiya
authors.forename: H G
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Y
authors.initials: Y
authors.lastname: Kaneko
authors.forename: M
authors.initials: M
authors.lastname: Takiguchi
mesh_terms: D000595:Amino Acid Sequence; D002478:Cells, Cultured; D015235:HLA-B Antigens / Q000737:chemistry*; D059949:HLA-B51 Antigen; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D014162:Transfection
chemical_list: D015235:HLA-B Antigens; D059949:HLA-B51 Antigen