Processing and delivery of peptides presented by MHC class I molecules

Effective MHC class I peptide loading requires the proteolytic degradation of cytosolic proteins and the TAP-mediated translocation of peptides across the membrane of the endoplasmic reticulum. The proteasome is emerging as the main cytosolic protease generating class I binding peptides. The recent elucidation of the proteasome crystal structure, together with the use of functional inhibitors, has enhanced our understanding of proteasome function. Genetic analysis of a novel mutant cell line emphasizes the importance of the TAP—class I interaction in the assembly of mature class I heterotrimers, and suggests that additional MHC-encoded components are required.