title: Thiol oxidation and reduction in MHC-restricted antigen processing and presentation.
abstract: Major histocompatibility complex (MHC) class I molecules are assembled in the endoplasmic reticulum (ER) as a trimer of the class I heavy chain, beta2 microglobulin (beta2m), and a short peptide. Assembly occurs in a complex with additional noncovalently associated proteins, which include the thiol oxidoreductase, ERp57. This molecule facilitates the formation of the correct disulfide bonds in glycoproteins as they fold in the ER and may play a key role in assembling a stable MHC class I-peptide complex. In the endocytic pathway, reduction of protein disulfide bonds is important for the generation of MHC class II-peptide complexes. This process is catalyzed by a gamma-interferon-inducible thiol reductase (GILT). The possible requirement for catalysis of disulfide bond formation in MHC class I-restricted antigen processing and the known requirement for disulfide bond reduction in MHC class II-restricted antigen processing present interesting examples of the adaptation of cellular "housekeeping" functions to facilitate immune responses.
authors.affiliation: Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520-8011, USA. peter.cresswell@qm.yale.edu
authors.forename: P
authors.initials: P
authors.lastname: Cresswell
authors.forename: B
authors.initials: B
authors.lastname: Arunachalam
authors.forename: N
authors.initials: N
authors.lastname: Bangia
authors.forename: T
authors.initials: T
authors.lastname: Dick
authors.forename: G
authors.initials: G
authors.lastname: Diedrich
authors.forename: E
authors.initials: E
authors.lastname: Hughes
authors.forename: M
authors.initials: M
authors.lastname: Maric
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D006360:Heat-Shock Proteins / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007535:Isomerases / Q000378:metabolism; D051379:Mice; D010084:Oxidation-Reduction; D019704:Protein Disulfide-Isomerases; D013438:Sulfhydryl Compounds / Q000378:metabolism*
chemical_list: D006360:Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D013438:Sulfhydryl Compounds; D007535:Isomerases; C513195:Pdia3 protein, mouse; D019704:Protein Disulfide-Isomerases