ENDOGENOUS ANTIGEN PRESENTATION BY MHC CLASS-II MOLECULES

T cell recognition of antigen requires that a complex form between pep tides derived from the protein antigen and cell surface glycoproteins encoded by genes within the major histocompatibility complex (MHC). MH C class II molecules present both extracellular (exogenous) and intern ally synthesized (endogenous) antigens to the CD4 T cell subset of lym phocytes. The mechanisms of endogenous antigen presentation are the su bject of this review. Isolation and amino acid sequencing of peptides bound to the class II molecule indicate that a very high proportion (7 0-90%) of the total peptides presented by the class II molecule are in fact derived from the pool of proteins that are synthetized within th e antigen-presenting cell (APC). This type of sequence information as well as the study of model antigens has indicated that proteins expres sed in a diversity of intracellular sites, including the cell surface, endoplasmic reticulum and cytosol can gain access to the class II mol ecule, albeit with different efficiencies. The main questions that rem ain to be answered are the intracellular trafficking patterns that all ow colocalization of internally synthesized antigens with the class II molecule, the site(s) within the cell where peptide:class II molecule complex formation can take place and whether presentation of 'foreign ' as well as 'self' antigens takes place by mechanisms that vary from one cell type to another or that vary with the metabolic state of the APC. If such variability exists, is would imply that the array of pept ides displayed by class II molecules at the cell surface has similar v ariability, a possibility that would impact on self tolerance and auto immunity.