ASSOCIATION WITH BIP AND AGGREGATION OF CLASS-II MCH MOLECULES SYNTHESIZED IN THE ABSENCE OF INVARIANT CHAIN

Class II molecules of the major histocompatibility complex (MHC) are c omposed of two polymorphic glycoprotein chains (alpha and beta), that associate in the ER with a third, non-polymorphic glycoprotein known a s the invariant chain (Ii). We have examined the relationship between the intracellular transport and physico-chemical characteristics of va rious combinations of murine alpha, beta and Ii chains. Biochemical an d morphological analyses of transfected fibroblasts expressing class I I MHC chains show that both unassembled alpha and beta chains, as well as a large fraction of alpha + beta complexes synthesized in the abse nce of Ii chain, are retained in the ER in association with the immuno globulin heavy chain binding protein, BiP. Analyses by sedimentation v elocity on sucrose gradients show that most incompletely assembled cla ss II MHC species exist as high molecular weight aggregates in both tr ansfected fibroblasts and spleen cells from mice carrying a disruption of the Ii chain gene. This is in contrast to the sedimentation proper ties of alpha beta Ii complexes from normal mice, which migrate as dis crete, stoichiometric complexes of M(r) similar to 200 000-300 000. Th ese observations suggest that assembly with the Ii chain prevents accu mulation of aggregated alpha and beta chains in the ER, which might re late to the known ability of the Ii chain to promote exit of class II MHC molecules from the ER.