Quality control of MHC class I maturation.
Assembly of MHC class I molecules in the ER is regulated by the so-called loading complex (LC). This multiprotein complex is of definite importance for class I maturation, but its exact organization and order of assembly are not known. Evidence implies that the quality of peptides loaded onto class I molecules is controlled at multiple stages during MHC class I assembly. We recently found that tapasin, an important component of the LC, interacts with COPI-coated vesicles. Biochemical studies suggested that the tapa-sin-COPI interaction regulates the retrograde transport of immature MHC class I molecules from the Golgi network back to the ER. Also other findings now propose that in addition to the peptide-loading control, the quality control of MHC class I antigen presentation includes the restriction of export of suboptimally loaded MHC class I molecules to the cell surface. In this review, we use recent studies of tapasin to examine the efficiency of TAP, the LC constitution, ER quality control of class I assembly, and peptide optimization. The concepts of MHC class I recycling and ER retention are also discussed.
Paulsson
Kajsa M
KM
Rayne Institute, Centre for Molecular Medicine, Department of Medicine, University College of London, 5 University St., London WC1E 6JJ, UK. k.paulsson@ucl.ac.uk
Wang
Ping
P
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D017920:Antiporters / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007136:Immunoglobulins / Q000502:physiology; D026901:Membrane Transport Proteins; D010455:Peptides / Q000378:metabolism; D021381:Protein Transport
D018528:ATP-Binding Cassette Transporters; D017920:Antiporters; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D010455:Peptides; C107762:tapasin