ER quality control in the biogenesis of MHC class I molecules.
Class I molecules of the major histocompatibility complex play a vital role in cellular immunity, reporting on the presence of viral or tumor-associated antigens by binding peptide fragments of these proteins and presenting them to cytotoxic T cells at the cell surface. The folding and assembly of class I molecules is assisted by molecular chaperones and folding catalysts that comprise the general ER quality control system which also monitors the integrity of the process, disposing of misfolded class I molecules through ER associated degradation (ERAD). Interwoven with general ER quality control are class I-specific components such as the peptide transporter TAP and the tapasin-ERp57 chaperone complex that supply peptides and monitor their loading onto class I molecules. This ensures that at the cell surface class I molecules will possess mainly optimal peptides with a long half-life. In this review we discuss these processes as well as a number of strategies that viruses have evolved to subvert normal class I assembly within the ER and thereby evade immune recognition by cytotoxic T cells.
Chapman
Daniel C
DC
Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
Williams
David B
DB
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006207:Half-Life; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008285:Major Histocompatibility Complex; D026901:Membrane Transport Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; D010446:Peptide Fragments; D010455:Peptides; C107762:tapasin; C477327:transporter associated with antigen processing (TAP)