title: Redox regulation of peptide receptivity of major histocompatibility complex class I molecules by ERp57 and tapasin.
abstract: The function of the oxidoreductase ERp57 in the major histocompatibility complex (MHC) class I peptide-loading complex has remained elusive. Here we show that in the absence of tapasin, the alpha2 disulfide bond in the MHC class I peptide-binding groove was rapidly reduced. Covalent sequestration of ERp57 by tapasin was needed to protect the alpha2 disulfide bond against reduction and thus to maintain the binding groove in a peptide-receptive state. Allelic variations in MHC class I tapasin dependency reflected their susceptibility to reduction of the alpha2 disulfide bond. In the absence of sequestration, ERp57 acted directly on the alpha2 disulfide bond. Our work provides insight into how the immune system customizes 'quality control' in the endoplasmic reticulum to fit the needs of antigen presentation.
authors.affiliation: Redox Regulation Research Group, German Cancer Research Center, D-69120 Heidelberg, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kienast
authors.forename: Marc
authors.initials: M
authors.lastname: Preuss
authors.forename: Monique
authors.initials: M
authors.lastname: Winkler
authors.forename: Tobias P
authors.initials: TP
authors.lastname: Dick
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D010084:Oxidation-Reduction; D019704:Protein Disulfide-Isomerases / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; C107762:tapasin; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human