ASSEMBLY, TRANSPORT, AND FUNCTION OF MHC CLASS-II MOLECULES

MHC class II molecules assemble in the endoplasmic reticulum in a chap erone-mediated fashion to form a nine-chain structure consisting of th ree alpha beta dimers associated with an invariant chain trimer. This complex is transported through the Golgi apparatus and into the endoso mal system. The signal for endosomal targeting resides in the cytoplas mic tail of the invariant chain. Current evidence argues that the segr egation of the class II-invariant chain complex from the constitutive pathway of membrane protein transport occurs in the trans-Golgi networ k. However, class II-invariant chain complexes that reach the cell sur face are also rapidly internalized into endosomes. Within the endosoma l system, probably in a late endosome/prelysosome, the invariant chain is degraded, releasing alpha beta dimers that bind peptides predomina ntly derived from endocytosed proteins. Evidence suggests that many of these peptides are actually generated in lysosomes. The precise mecha nisms involved in forming class II-peptide complexes are unclear, alth ough the existence of antigen-processing mutants argues that additiona l gene products, at least one of which is encoded in the MHC, are invo lved. After binding peptides, class II molecules are transported by an unknown route to the cell surface, where their primary function of pr esenting antigenic peptides to CD4(+) T cells is carried out.