title: Identification of HLA-DR4-restricted immunogenic peptide derived from xenogenic porcine major histocompatibility complex class I molecule.
abstract: Indirect recognition of xenoantigens has been implicated as the major mechanism underlying xenospecific CD4+ T-cell activation in chronic rejection. We identified swine leukocyte antigen (SLA)-derived immunogenic peptides that are presented in the context of human HLA-DR4 molecules. The SLA class I-derived peptides that bind HLA-DRB1*0401, a representative of the DR4 supertype, were predicted using a computer-assisted algorithm. The candidate peptides were synthesized, and their binding capacities to HLA-DRB1*0401 were compared in a competitive ELISA using biotinylated hemagglutinin reporter peptides [HA(307-319)]. Peptide-11 (LRSWTAADTAAQISK) was determined to exhibit the most potent binding capacity to HLA-DRB1*0401 in vitro and thus selected for in vivo immunization. Immunization of HLA-DRB1*0401-transgenic mice with peptide-11 elicited potent CD4+ Th1 responses. Peptide-11 shares homology to α2 domains of three SLA-1 alleles, six SLA-2 alleles, and 14 SLA-3 alleles. Thus, this study has important implications not only for the identification of an immunogenic indirect epitope shared by diverse SLA class I alleles, but also for the development of epitope-specific immunoregulation strategies.
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, South Korea.
authors.forename: Chan-Su
authors.initials: CS
authors.lastname: Park
authors.forename: Ki-Hyang
authors.initials: KH
authors.lastname: Kim
authors.forename: Sun-A
authors.initials: SA
authors.lastname: Im
authors.forename: Sukgil
authors.initials: S
authors.lastname: Song
authors.forename: Chong-Kil
authors.initials: CK
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000910:Antibodies, Heterophile / Q000096:biosynthesis; D015478:Antigens, Heterophile / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D015804:HLA-DR4 Antigen / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D034421:Sus scrofa / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014183:Transplantation, Heterologous
chemical_list: D000910:Antibodies, Heterophile; D015478:Antigens, Heterophile; D018984:Epitopes, T-Lymphocyte; D015804:HLA-DR4 Antigen; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; C438668:swine leukocyte antigen