title: Identification of HLA-DR9 (DRB1*0901)-binding peptide motifs using a phage fUSE5 random peptide library.
abstract: We identified HLA-DRB1*0901-binding peptides by affinity-based selection of a phage random peptide library using the biotinylated DR9 complex. Analogue peptides with single amino acid residue substitutions of a DR9 binder revealed that two major anchors (WxxS, where x is any amino acid) play an essential role in binding to DR9. Determination of the binding affinity of synthetic wild-type-based analogue peptides showed that substituting W to F or L, and S to A, V, or F allow high affinity binding with DR9. Collectively, DR9-binding peptide motifs identified in this study are characteristic in that (a) only two anchors of the NH2-terminal half of binding peptides play important roles in binding, and (b) small neutral hydrophilic Ser is allowed as the second anchor for high-affinity binding, unlike the other DR-binding motifs heretofore reported. The implications of our results are discussed in light of the HLA-DR9-associated susceptibility to juvenile-onset myasthenia gravis and systemic lupus erythematosus with antiphospholipid syndrome, in particular, T-cell responses to autoantigens.
authors.affiliation: Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fujisao
authors.forename: S
authors.initials: S
authors.lastname: Matsushita
authors.forename: T
authors.initials: T
authors.lastname: Nishi
authors.forename: Y
authors.initials: Y
authors.lastname: Nishimura
mesh_terms: D000595:Amino Acid Sequence; D002999:Clone Cells; D003090:Coliphages / Q000235:genetics / Q000276:immunology*; D015723:Gene Library; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000302:isolation & purification* / Q000378:metabolism*; D059810:HLA-DR Serological Subtypes; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000096:biosynthesis / Q000302:isolation & purification* / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology
chemical_list: D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C038988:HLA-DR9 antigen; D010446:Peptide Fragments