A ROLE FOR CALNEXIN (IP90) IN THE ASSEMBLY OF CLASS-II MHC MOLECULES

Major histocompatibility complex (MHC) class II antigens consist of alpha and beta chains that associate intracellularly with the invariant (I) chain. The HLA-DR alphabetaI complex assembles in the endoplasmic reticulum (ER) into a nonameric structure via progressive addition of three alphabeta dimers to a core invariant chain trimer. We have examined intracellular association of alphabetaI complexes with the resident ER protein calnexin. Calnexin associates rapidly (within 3 min) with newly synthesized alpha, beta and I chains, and remains associated with the assembling alphabetaI complex until the final alphabeta dimer is added, forming the complete nonamer. Dissociation of calnexin parallels egress of alphabetaI from the ER. These results suggest that calnexin retains and stabilizes both free class II subunits and partially assembled class II - I chain complexes until assembly of the nonamer is complete.