Major histocompatibility complex class I-ERp57-tapasin interactions within the peptide-loading complex.
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.
Santos
Susana G
SG
Bute Medical School, University of St. Andrews, Fife KY16 9TS, Scotland, United Kingdom.
Campbell
Elaine C
EC
Lynch
Sarah
S
Wong
Vincent
V
Antoniou
Antony N
AN
Powis
Simon J
SJ
D000818:Animals; D002460:Cell Line; D004220:Disulfides / Q000737:chemistry; D005805:Genes, MHC Class I; D006801:Humans; D008285:Major Histocompatibility Complex; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008970:Molecular Weight; D046912:Multiprotein Complexes; D010084:Oxidation-Reduction; D010455:Peptides / Q000378:metabolism*; D011487:Protein Conformation; D019704:Protein Disulfide-Isomerases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D001613:beta 2-Microglobulin / Q000378:metabolism
D004220:Disulfides; D026901:Membrane Transport Proteins; D046912:Multiprotein Complexes; D010455:Peptides; D001613:beta 2-Microglobulin; C107762:tapasin; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human