Assembly of MHC class I molecules within the endoplasmic reticulum.
MHC class I molecules bind cytosolically derived peptides within the endoplasmic reticulum (ER) and present them at the cell surface to cytotoxic T cells. A major focus of our laboratory has been to understand the functions of the diverse proteins involved in the intracellular assembly of MHC class I molecules. These include the molecular chaperones calnexin and calreticulin, which enhance the proper folding and subunit assembly of class I molecules and also retain assembly intermediates within the ER; ERp57, a thiol oxidoreductase that promotes heavy chain disulfide formation and proper assembly of the peptide loading complex; tapasin, which recruits class I molecules to the TAP peptide transporter and enhances the loading of high affinity peptide ligands; and Bap31, which is involved in clustering assembled class I molecules at ER exit sites for export along the secretory pathway. This review describes our contributions to elucidating the functions of these proteins; the combined effort of many dedicated students and postdoctoral fellows.
Zhang
Yinan
Y
Departments of Biochemistry and Immunology, University of Toronto Toronto, Ontario, Canada.
Williams
David B
DB
D000818:Animals; D037281:Calnexin / Q000502:physiology; D037282:Calreticulin / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D026901:Membrane Transport Proteins / Q000502:physiology; D051379:Mice; D011487:Protein Conformation; D019704:Protein Disulfide-Isomerases / Q000502:physiology
C091247:BCAP31 protein, human; D037282:Calreticulin; D006360:Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C107762:tapasin; D037281:Calnexin; C513195:Pdia3 protein, mouse; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human