title: An HLA-binding-motif-aided peptide epitope library: a novel library design for the screening of HLA-DR4-restricted antigenic peptides recognized by CD4+T cells.
abstract: Susceptibility to a series of autoimmune diseases is strongly associated with particular HLA class II alleles. Identification of T cell clones and antigenic epitopes bound by HLA class II molecules involved in autoimmune diseases is critical to understanding the etiology of these HLA class II-associated diseases. However, establishment of T cell clones in autoimmune diseases is difficult because the antigenic peptides are unknown. Peptide library methods which include all possible peptide sequences offer a potentially powerful tool for the detection of cross-reactive antigenic peptides recognized by T cells. Here, we reduced the number of peptides per mixture by utilizing the known binding motifs of peptides for the HLA-DRB1*0405 molecule and evaluated the effectiveness of this library design. Each library mixture evoked a strong proliferative response in the unprimed peripheral blood lymphocytes (PBL) from HLA-DRB1*0405-positive donors but little or no response in the PBL from HLA-DRB1*0405-negative donors. The library also detected antigenic peptides that activated three antigen-specific T cell lines restricted by HLA-DRB1*0405, with different specificities. The motif-based approach thus presents a powerful method for monitoring T cells in large, heterogeneous T cell populations and is useful for the identification of the mimic peptide epitopes of T cell lines and clones.
authors.affiliation: Department of Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tana
authors.forename: N
authors.initials: N
authors.lastname: Kamikawaji
authors.forename: C J
authors.initials: CJ
authors.lastname: Savoie
authors.forename: T
authors.initials: T
authors.lastname: Sudo
authors.forename: Y
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: T
authors.initials: T
authors.lastname: Sasazuki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000737:chemistry* / Q000378:metabolism; D015804:HLA-DR4 Antigen / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007739:L Cells; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D014162:Transfection
chemical_list: D000939:Epitopes; D015804:HLA-DR4 Antigen; D019151:Peptide Library; D010455:Peptides