Identification of HLA‐DR4‐restricted immunogenic peptide derived from xenogenic porcine major histocompatibility complex class I molecule

Park C‐S, Kim K‐H, Im S‐A, Song S, Lee C‐K. Identification of HLA‐DR4‐restricted immunogenic peptide derived from xenogenic porcine major histocompatibility complex class I molecule. Xenotransplantation 2012; 19: 317–322. © 2012 John Wiley & Sons A/S. 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.