ANTIGEN PRESENTATION BY MHC CLASS-II MOLECULES

The tremendous explosion in the field of MHC research in the last 5 ye ars has significantly advanced our understanding of antigen processing pathways, particularly with regard to details of MHC class II-mediate d antigen presentation. MHC class II molecules at the surface of antig en presenting cells present antigenic peptides to CD4(+) T helper cell s. However for effective cell surface antigen presentation, a number o f highly synchronized events must first take place intracellularly. Th e monomorphic protein, invariant chain (Ii), is a crucial participant in MHC class II antigen presentation. Acting as a molecular chaperone, this molecule escorts the newly synthesized class II heterodimers fro m the endoplasmic reticulum into the endosomal system. During this man oeuvre, the interaction of Ii with class IL serves to prevent prematur e association of antigenic peptide. Once the complex reaches the acidi c environment of the endosomes, Ii is proteolytically degraded and dis sociates, leaving the class II binding site available for binding anti genic peptide derived from exogenous proteins. The final Ii fragment t o be displaced, CLIP (class II-associated invariant chain peptides), m ust be physically removed from the class II binding groove with assist ance from another MHC-encoded molecule, DM. The interaction of DM with class II also aids in the subsequent rapid loading of high-affinity a ntigen-derived peptides into the MHC class II groove. The stable pepti de-loaded complexes are now ready to exit the endocytic compartments t o present their peptide antigen to specific T helper cells at the cell surface.