Pitch session 1Large-scale immunopeptidome analysis shed new light on the antigen processing and presentation

Abstract

Antigen processing and presentation are thought to begin with proteolysis in the proteasome, transport through TAP to the ER, trimming by ERAP1/2, loading assisted by ER chaperones, and transport by the MHC of selected peptides according to their affinities. Large-scale peptidome analysis based on LC-MS/ MS and dynamic heavy isotope amino acids labeling of the HLA peptidome and the cellular proteome shed new light on some of the steps in this pathway 1,2 . The relative contribution of the contribution of the proteasome 1 , the effect of the TAP and ERAP1 3 on the HLA peptidome were investigated using the dynamic immunopeptidome analysis. The results of the analysis suggest somewhat different mechanism and limiting factors than the currently accepted. The contribution of the proteasome seems to be lower than expected (1); ERAP1 affects only a subset of the HLA peptidome 3,4 and TAP inhibition does not block presentation of cytoplasmic peptides. Thus, I suggest reconsidering the APP process based on this data.