THE ROLE OF THE INVARIANT CHAIN IN MUCOSAL IMMUNITY

The invariant chain (Ii) due to its intimate association with major hi stocompatibility complex (MHC) alpha and beta chains is a determining element in the development of immune responses. Ii plays a major role in the assembly, the intracellular transport and peptide selection by class II MHC. A segment of Ii designated as CLIP (class II-associated Ii peptide) binds into the antigen binding site of class II MHC molecu les until class II MHC reach intracellular compartments that contain p eptides from internalized antigens. This association limits the self e ndogenous peptides that can bind to class II MHC molecules. The remova l of CLIP from class II MHC catalyzes the binding of antigenic peptide s and their subsequent cell surface expression. An isoform of Ii, know n as chondroitin sulfate-modified Ii (IiCS), that is surface-expressed enhances T cell activation while acting as a coreceptor for CD44. The expression of class II MHC molecules by mucosal epithelial cells has generated interest in the role that these cells may have in mucosal im munity. Since in classical antigen-presenting cells (APC) the biology of class II MHC is regulated by Ii, it is necessary to bring into pers pective the known functions of Ii in conventional APC to understand th e role that Ii may play in mucosal epithelial cells as potential regul ators of local immune responses.