Redox-regulated peptide transfer from the transporter associated with antigen processing to major histocompatibility complex class i molecules by protein disulfide isomerase

Kwangmin Cho, Sunglim Cho, Seong Ok Lee, Changhoon Oh, Kwonyoon Kang, Jeongmin Ryoo, Sungwook Lee, Seongman Kang, Kwangseog Ahn

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Most antigenic peptides are generated by proteasomes in the cytosol and are transported by the transporter associated with antigen processing (TAP) into the endoplasmic reticulum, where they bind with nascent major histocompatibilitiy complex class I molecule (MHC-I). Although the overall process of peptide-MHC-I complex assembly is well studied, the mechanism by which free peptides are delivered from TAP to MHC-I is unknown. In this study, we investigated the possible role of protein disulfide isomerase (PDI) as a peptide carrier between TAP and MHC-I. Analysis of PDI-peptide complexes reconstituted in vitro showed that PDI exhibits some degree of specificity for peptides corresponding to antigenic ligands of various human leukocyte antigen (HLA) alleles. Mutations of either anchor residues of the peptide ligand or the peptide-binding site of PDI inhibited the PDI-peptide interaction. The PDI-peptide interaction increased under reducing conditions, whereas binding of the peptide to PDI decreased under oxidizing conditions. TAP-associated PDI was predominantly present in the reduced form, whereas the MHC-I-associated PDI was present in the oxidized form. Further, upon binding of optimal peptides, PDI was released from TAP and sequentially associated with HLA-A2.1. Our data revealed a redox-regulated chaperone function of PDI in delivering antigenic peptides from TAP to MHC-I.

Original languageEnglish
Pages (from-to)621-633
Number of pages13
JournalAntioxidants and Redox Signaling
Volume15
Issue number3
DOIs
Publication statusPublished - 2011 Aug 1

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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