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

Major histocompatibility complex (MHC) class II antigens consist of al pha 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 exami ned intracellular association of alphabetaI complexes with the residen t ER protein calnexin. Calnexin associates rapidly (within 3 min) with newly synthesized alpha, beta and I chains, and remains associated wi th the assembling alphabetaI complex until the final alphabeta dimer i s added, forming the complete nonamer. Dissociation of calnexin parall els egress of alphabetaI from the ER. These results suggest that calne xin retains and stabilizes both free class II subunits and partially a ssembled class II - I chain complexes until assembly of the nonamer is complete.