A revised model for invariant chain-mediated assembly of MHC class II peptide receptors.

The enormous number of allelic MHC class II glycoproteins provides the immune system with a large set of heterodimeric receptors for the binding of pathogen-derived peptides. How do inherited allo- or isotypic subunits of MHC class II combine to produce such a variety of functional peptide receptors? We propose a new mechanism in which pairing of matched MHC class II alpha- and beta-subunits is coordinated by the invariant chain chaperone. The assembly is proposed to occur in a sequential fashion, with a matched beta-chain being selected by the alpha-chain-invariant chain 'scaffold' complex that is formed first. This sequential assembly is a prerequisite for subsequent intracellular transport of the alpha-chain-invariant chain-beta-oligomer and its maturation into a functional peptide receptor.