Identification of HLA-A2-restricted immunogenic peptides derived from a xenogenic porcine major histocompatibility complex

Xenotransplantation. 2014 Sep-Oct;21(5):465-72. doi: 10.1111/xen.12119. Epub 2014 Jul 8.

Abstract

Background: Little information is available regarding the precise swine leukocyte antigen (SLA)-derived immunogenic peptides that are presented in the context of human HLA molecules. Here, we identified SLA-derived immunogenic peptides that are presented in association with human HLA-A2 molecule.

Methods: 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 peptides and HLA-A*0201 were compared using major histocompatibility complex (MHC) stabilization assays. The cytotoxic T lymphocyte (CTL)-inducing activity of the selected peptides was examined in HLA-A*0201-transgenic mice.

Results: 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 α2 domains of 34 SLA-1 alleles, 18 SLA-2 alleles, and 1 SLA-3 allele.

Conclusion: This study identifies an immunogenic HLA-A*0201-restricted epitope derived from the SLA, which may be valuable for the development of epitope-specific immunoregulation strategies.

Keywords: HLA-A2; indirect recognition; swine leukocyte antigen; xenorecognition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Epitopes, T-Lymphocyte / immunology*
  • HLA-A2 Antigen / immunology*
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II / immunology*
  • Humans
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Transgenic
  • Swine
  • Transplantation, Heterologous

Substances

  • Epitopes, T-Lymphocyte
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • swine leukocyte antigen