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

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-DRB10401, a representative of the DR4 supertype, were predicted using a computer-assisted algorithm. The candidate peptides were synthesized, and their binding capacities to HLA-DRB10401 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-DRB10401 in vitro and thus selected for in vivo immunization. Immunization of HLA-DRB10401-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.