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 tapasin-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.