Endogenous pathway of class II presentation

Assembly, targeting and peptide loading of MHC class II molecules is controlled by a series of mechanisms and molecular interactions that inhibit the binding of peptides or proteins in the ER or secretory compartment. As a consequence, the major site of peptide binding to class II molecules is in the endosomal/lysosomal compartment. The barrier, however, between exogenous and endogenous antigen presentation by MHC class II molecules does not seem to be as tight as for MHC class I, and several different mechanisms may contribute to MHC class II presentation of endogenous antigens. Although limited, the possibility of presentation of endogenous antigens may nevertheless be important in viral infections and in tumours, for the recruitment of CD4-positive helper T-cells. This may also apply when unfolded or misfolded proteins accumulate in the ER and compete with the invariant chain for binding to MHC class II molecules. The potential relevance of this pathway to triggering autoimmune reactions has yet to be explored.