Exogenous Pathway of Antigen Presentation | MHC II Processing

Antigens from the extracellular space and sometimes also endogenous ones,[8] are enclosed into endocytic vesicles and presented on the cell surface by MHC-II molecules to the helper T cells expressing CD4 molecule. Only APCs do express the class II of MHC molecules on the surface in large quantity, such as dendritic cells, B cells or macrophages, so expression of MHC-II molecules is more cell-specific than MHC-I.

APCs usually internalise exogenous antigens by endocytosis, but also by pinocytosis, macroautophagy, endosomal microautophagy or chaperone-mediated autophagy. In the first case, after internalisation, the antigens are enclosed in vesicles called endosomes. There are three compartements involved in this antigen presentation pathway: early endosomes, late endosomes or endolysosomes and lysosomes, where antigens are hydrolized by lysosome-associated enzymes (acid-dependent hydrolases, glycosidases, proteases, lipases). This process is favored by gradual reduction of the pH. The main proteases in endosomes are cathepsins and the result is the degradation of the antigens into oligopeptides.

MHC-II molecules are transported from the ER to the MHC class II loading compartment together with the protein Invariant chain (Ii, CD74). A non classical MHC-II molecule (HLA-DO and HLA-DM) catalyses the exchange of part of the CD74 (CLIP peptide) with the peptide antigen.