Computational prediction and functional identification of HLA-A2-restricted T lymphocyte epitopes derived from swine leukocyte antigen (TRAN2P.962)

Abstract Xenotransplantation using porcine organs is a potential solution to the problem of the shortage of allografts. However, immunological rejection of xenografts remains as a major hurdle to success. Little information is available regarding the precise swine leukocyte antigen (SLA)-derived immunogenic peptides that are presented in the context of human HLA molecules. The SLA-derived peptides that bind to HLA-A*0201, a representative of the A2 supertype, were predicted using a computer-assisted algorithm. The candidate peptides were synthesized, and the stabilities of complexes formed between the peptides and HLA-A*0201 were compared using MHC stabilization assays. The cytotoxic T lymphocyte (CTL)-inducing activity of the selected peptides was examined in HLA-A*0201-transgenic mice. Among 15 candidate peptides synthesized, two peptides, peptide-35 (YLGPDGLLL) and peptide-43 (TLICHVDSI), were selected to have high affinity and stability with HLA-A*0201. Examination of the CTL-inducing activity of the two peptides in HLA-A*0201-transgenic mice showed that immunization with peptide-35, but not peptide-43, elicited potent CD8-specific-CTL responses. The Peptide-35 is present in non-polymorphic a2 domains of 34 SLA-1 alleles, 18 SLA-2 alleles, and 1 SLA-3 allele. These results show that Peptide-35 is a HLA-A2-restricted immunogenic peptide derived from SLA.