Supply and transport of peptides presented by class I MHC molecules

Three observations suggest that the proteasome, transporter associated with antigen processing (TAP) and class I MHC molecules are co-adapted for the generation, transport and loading of specific peptides. Firstly, TAP preferentially transport peptides close in length to the optimum for class I loading; secondly, genetic variation in TAP specificity focusing in the carboxy-terminal of the peptide correlates with preferences among class I molecules for different peptide carboxy-termini; thirdly, TAP associates directly with empty class I molecules and is released by succesful peptide loading. This conclusion puts in question the significance for class I loading of proteolytic processing and peptide generation in the endoplasmic reticulum.