MHC Class II Processing

MHC (major histocompatibility complex) Class II molecules are found only on a few specialized cell types, including macrophages, dendritic cells and B cells, all of which are professional antigen-presenting cells (APCs).The peptides presented by class II molecules are derived from extracellular proteins (not cytosolic as in class I); hence, the MHC class II-dependent pathway of antigen presentation is called the endocytic or exogenous pathway

Synthesis

During synthesis, MHC class II is the result of dimerization of α and β chains, with the assistance of an invariant chain.[2] The invariant chain is a special polypeptide involved in the formation and deliverance of MHC class II protein.

The nascent MHC class II protein in the rough ER has its peptide-binding cleft blocked by the invariant chain (Ii; a trimer) to prevent it from binding cellular peptides or peptides from the endogenous pathway. The invariant chain also facilitates MHC class II's export from the ER in a vesicle. This fuses with a late endosome containing the endocytosed, degraded proteins. It is then broken down in stages, leaving only a small fragment called CLIP which still blocks the peptide binding cleft. An MHC class II-like structure, HLA-DM, removes CLIP and replaces it with a peptide from the endosome. The stable MHC class-II is then presented on the cell surface.