Human immune responses to porcine endogenous retrovirus-derived peptides presented naturally in the context of porcine and human major histocompatibility complex class I molecules: implications in xenotransplantation of porcine organs

Transplantation
Sabarinathan RamachandranT Mohanakumar

Abstract

Porcine endogenous retroviruses (PERV) have been shown to infect human cells, raising concerns regarding safety of xenotransplantation. In patients exposed to porcine tissues, no PERV infection has been observed. This study was designed to develop human CD8+ cytotoxic T lymphocytes (CTL) against PERV-derived peptides presented in the context of human leukocyte antigen (HLA) or swine leukocyte antigen (SLA) class I molecules and to define dominant epitopes contributed by PERV. Human CD8+ CTL were generated against porcine aortic endothelial cells (PAEC). Peptides presented on SLA class I molecules were acid eluted and fractionated by reverse-phase high-performance liquid chromatography. Peptide fractions that restored lysis of acid-stripped PAEC were sequenced by tandem mass spectrometry. Human CD8+ CTL were generated against PERV envelope-derived peptides and PERV-infected human cells to identify immunodominant PERV-derived epitopes. We identified two peptides derived from retroviral transactivating regulatory protein (AHQDPLPEQP) and retroviral transcription factor (PQKPFVT) recognized by human CD8+ CTL in the context of SLA class I. Computer-assisted analysis identified nine PERV-envelope-derived 9-mer peptides with high affi...Continue Reading

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Citations

Sep 2, 2008·Developmental and Comparative Immunology·Joan K LunneyDouglas M Smith
Oct 14, 2004·Xenotransplantation·Reto M Baertschiger, Leo H Buhler
Jun 14, 2008·International Journal of Immunogenetics·Y J LeeJ H Lee
Dec 18, 2019·Annual Review of Animal Biosciences·Sabine E HammerJoan K Lunney
Jul 31, 2020·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·A B SmulevichE I Voronova

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