title: A single amino acid change makes the peptide specificity of B*3910 unrelated to B*3901 and closer to a group of HLA-B proteins including the malaria-protecting allotype HLA-B53.
abstract: HLA-B*3910, which has only been found in African and African American individuals, differs from B*3901 by the single amino acid change of Cys67 to Tyr67. Sequence analysis of the B*3910-bound peptide pool and of several individual ligands revealed that this subtype has strong preference for peptides with Pro2. This is in contrast with the preference of B*3901 for peptides with basic residues (Arg and His) at this position, and indicates that the single amino acid substitution between B*3910 and B*3901 totally changes the repertoire of bound peptides. This is presumably due to the significant decrease in the size of the B pocket, and to its increased hydrophobicity, since Tyr67 takes part in this pocket. B*3910 is similar to various other class I proteins in its preference for peptides with Pro2 and nonpolar C-terminal residues, including HLA-B53, an antigen associated with protection against severe malaria. The role of these two motifs as major peptidic anchors suggests that B*3910 and HLA-B53 may bind common peptides.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Facultad de Ciencias, Cantoblanco, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Yagüe
authors.forename: J
authors.initials: J
authors.lastname: Vázquez
authors.forename: J A
authors.initials: JA
authors.lastname: López de Castro
mesh_terms: D019943:Amino Acid Substitution; D006680:HLA Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000737:chemistry / Q000276:immunology*; D059946:HLA-B39 Antigen; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000276:immunology; D008288:Malaria / Q000276:immunology*; D010455:Peptides / Q000235:genetics* / Q000276:immunology*; D013329:Structure-Activity Relationship
chemical_list: D006680:HLA Antigens; D015235:HLA-B Antigens; D059946:HLA-B39 Antigen; C078438:HLA-B53 antigen; D007126:Immunoglobulin Allotypes; D010455:Peptides