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 language | English |
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Pages (from-to) | 17587-17593 |
Number of pages | 7 |
Journal | Journal of Biological Chemistry |
Volume | 282 |
Issue number | 24 |
DOIs | |
Publication status | Published - 15 Jun 2007 |
Keywords
- MHC CLASS-I
- DEPENDENT REDUCTASE ERP57
- ENDOPLASMIC-RETICULUM
- OXIDOREDUCTASE ERP57
- HEAVY-CHAIN
- CELL-LINE
- MOLECULES
- TAPASIN
- HLA-B27
- TAP