A role for calnexin (IP90) in the assembly of class II MHC molecules

Abstract

Major histocompatibility complex (MIC) class II antigens consist of α and β chains that associate intracellularly with the invariant (I) chain. The HLA-DR αβI complex assembles in the endoplasmic reticulum (ER) into a nonameric structure via progressive addition of three αβ dimers to a core invariant chain trimer. We have examined intracellular association of αβI complexes with the resident ER protein calnexin. Calnexin associates rapidly (within 3 min) with newly synthesized α, β and I chains, and remains associated with the assembling αβI complex until the final αβ dimer is added, forming the complete nonamer. Dissociation of calnexin parallels egress of αβI 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.