Major Histocompatibility Complex cCass I-ERp57-Tapasin Interactions within the Peptide-loading Complex.

S.G Santos, E.C Campbell, S Lynch, V Wong, A.N Antoniou, Simon John Powis

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

The endoplasmic reticulum-located multimolecular peptide-loading complex functions to load optimal peptides onto major histocompatibility complex ( MHC) class I molecules for presentation to CD8(+) T lymphocytes. Two oxidoreductases, ERp57 and protein-disulfide isomerase, are known to be components of the peptide-loading complex. Within the peptide-loading complex ERp57 is normally found disulfide-linked to tapasin, through one of its two thioredoxin-like redox motifs. We describe here a novel trimeric complex that disulfide links together MHC class I heavy chain, ERp57 and tapasin, and that is found in association with the transporter associated with antigen processing peptide transporter. The trimeric complex normally represents a small subset of the total ERp57-tapasin pool but can be significantly increased by altering intracellular oxidizing conditions. Direct mutation of a conserved structural cysteine residue implicates an interaction between ERp57 and the MHC class I peptide-binding groove. Taken together, our studies demonstrate for the first time that ERp57 directly interacts with MHC class I molecules within the peptide-loading complex and suggest that ERp57 and protein-disulfide isomerase act in concert to regulate the redox status of MHC class I during antigen presentation.

Original languageEnglish
Pages (from-to)17587-17593
Number of pages7
JournalJournal of Biological Chemistry
Volume282
Issue number24
DOIs
Publication statusPublished - 15 Jun 2007

Keywords

  • MHC CLASS-I
  • DEPENDENT REDUCTASE ERP57
  • ENDOPLASMIC-RETICULUM
  • OXIDOREDUCTASE ERP57
  • HEAVY-CHAIN
  • CELL-LINE
  • MOLECULES
  • TAPASIN
  • HLA-B27
  • TAP

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