title: Refined peptide HLA-B*3501 binding motif reveals differences in 9-mer to 11-mer peptide binding.
abstract: HLA-B*3501 is associated with subacute thyroiditis and fast progression of AIDS. An important prerequisite to investigate the T-cell recognition of HLA-B*3501-restricted antigens is the characterization of peptide-HLA-B*3501 interactions. In this study, peptide-HLA-B*3501 interactions were determined in quantitative peptide binding assays. The results were statistically analyzed to evaluate the influence of both anchor and nonanchor positions and the predictability of peptide binding. The binding data demonstrated that all anchor residues at position 2 and the C-terminus found in 9-mers functioned equally as anchors in 10-mers and 11-mers. These minimum requirements of peptide binding were refined by assessing positive and negative effects of nonanchor residues. Aliphatic hydrophobic residues at positions 3, 5, and 8 of 10-mers and position 3 of 11-mers significantly enhanced HLA-B*3501 binding. Similar effects rendered aromatic, bulky residues, acidic or polar residues of 11-mers at position 1 as well as at positions 4, 8, and 10, respectively. Negative effects were observed for residues carrying positively charged side-chains at position 7 of 11-mers. The refined HLA-B*3501 peptide binding motifs enhanced the identification of potential T-cell epitopes. The disparity between positive effects at the middle and C-terminal part (positions 5 - 8 and 10) of 11-mers and shorter peptides supports the extrusion of 11-mer residues at positions 5, 6, and 7, away from the HLA-B*3501 binding cleft.
authors.affiliation: Department of Tumor Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Schönbach
authors.forename: K
authors.initials: K
authors.lastname: Miwa
authors.forename: M
authors.initials: M
authors.lastname: Ibe
authors.forename: H
authors.initials: H
authors.lastname: Shiga
authors.forename: K
authors.initials: K
authors.lastname: Nokihara
authors.forename: M
authors.initials: M
authors.lastname: Takiguchi
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D015797:HLA-B35 Antigen / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data
chemical_list: D015797:HLA-B35 Antigen