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

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.

journal_name

Xenotransplantation

journal_title

Xenotransplantation

authors

Park CS,Im SA,Song S,Kim K,Lee CK

doi

10.1111/xen.12119

subject

Has Abstract

pub_date

2014-09-01 00:00:00

pages

465-72

issue

5

eissn

0908-665X

issn

1399-3089

journal_volume

21

pub_type

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