TRANSIENT AGGREGATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II CHAINS DURING ASSEMBLY IN NORMAL SPLEEN-CELLS

Many cell surface proteins exist as complexes of multiple subunits. It is well established that most such complexes are assembled within the endoplasmic reticulum (ER). However, the mechanistic details of the a ssembly process are largely unknown. We show here that alpha and beta subunits of major histocompatibility complex class II antigens in sple en cells of normal mice pass through a transiently aggregated phase in the ER prior to assembly with the invariant chain (Ii). Aggregates fo rm immediately after synthesis and disappear concomitantly with assemb ly of mature alpha beta Ii complexes. In spleen cells lacking Ii, aggr egates fail to be efficiently dissociated over time, implicating subun it assembly as a requirement for disaggregation. Two ER chaperones, Bi P and calnexin, bind to newly synthesized class II MHC chains but do n ot contribute appreciably to the large size of the aggregates. Our obs ervations suggest that some subunits of multisubunit complexes pass th rough a transient, dynamic high molecular weight aggregate phase durin g the physiological process of assembly. The results further suggest a novel role for Ii in promoting stable dissociation of preformed aggre gates containing alpha and beta subunits rather than in preventing the ir formation.