HOW MHC CLASS-II MOLECULES ACQUIRE PEPTIDE CARGO - BIOSYNTHESIS AND TRAFFICKING THROUGH THE ENDOCYTIC PATHWAY

The antigen-specific receptors of T lymphocytes rely on products of th e major histocompatibility complex (MHC) to recognize and engage antig en. MHC molecules display antigen on the cell surface in the form of s mall peptides, generated intracellularly by fragmentation of the intac t protein antigen. They acquire these peptides at distinct intracellul ar locations: In the endoplasmic reticulum (ER), class I molecules bin d peptides derived from cytosolic proteins, whereas class II molecules acquire their peptide cargo in an endocytic compartment. Sequestratio n of class II molecules from the constitutive secretory pathway is med iated by their interaction with an additional polypeptide, the invaria nt chain (Ii). The Ii contains sorting signals in its cytoplasmic tail that target class II molecules to the endocytic pathway where they en counter peptides generated from protein antigens that have also access ed this route.