Identification of swine leukocyte antigen-derived peptides inducing epitope-specific CTL responses in HLA-A2 transgenic mice (TRAN3P.882)

Xenotransplantation of porcine organ is considered a potential solution to the problem of allograft shortage. A xenograft is rejected by cross-primed CD8 cytotoxic T cells as these cells show cytotoxicity against xenografts by recognition of swine leukocyte antigen (SLA). However, the precise swine leukocyte antigen (SLA)-derived immunogenic peptides that are presented in the context of human HLA molecules remain to be elucidated. In the present study, 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 then the stability of peptide/HLA-A*0201 complexes was compared by MHC stabilization assays using HLA-A*0201-expressing Tap knock out T2 cells. Of 15 candidate peptides, two peptides, peptide-35 and peptide-43, were selected to have high affinity and stability with HLA-A*0201. Immunization of HLA- A*0201-transgenic mice with peptide-35 elicited potent CD8 CTL cell responses, while immunization with peptide-43 did not induce noticeable CTL responses. Induction of peptide-35-specific CD8 T cells was also confirmed by intracellular IFN-g staining of CD8 T cells from peptide-35 primed mice. This study has important implications not only for the identification of an immunogenic HLA-A*0201-restricted indirect epitope derived from SLA, but also for the development of epitope-specific immunoregulation strategies.