Invariant chain influences post-translational processing of HLA-DR molecules

HLA class II MHC molecule α- and β-chains are normally synthesized in the presence of a third molecule, the invariant chain (Ii). Although Ii is not required for surface expression of HLA class II molecules, the influence of Ii on post-translational proccessing and maturation HLA class II molecules has not been thoroughly studied. In the present study, BALB/c 3T3 cells were transfected with HLA-DR α-and β-chains with or without co-transfection with human Ii. Although Ii had no effect on the surface expression of DR, Ii did have a profound effect on the post-translational processing of both the α- and β-chains. In the absence of Ii, the major species of α- and β-chains were of lower m.w. than when expressed in the presence of Ii. The differences in m.w. were shown to be caused by differences in glycosylation with the majority of α- and β-chains remaining unprocessed and endo H sensitive in the absence of Ii. The small proportion of α-chains that were processed in the absence of Ii showed an altered m.w. and altered sensitivity to treatment with endo H relative to α-chains processed in the presence of Ii. Pulse/chase studies demonstrated that although the majority of the α- and β-chains remained unprocessed in the absence of Ii, the small amount that was processed was done so at a rate similar to that observed for α- and β-chains processed in the presence of Ii. These studies demonstrate that Ii influences the post-translational processing of human class II molecules by affecting the proportion of α-and β-chains that are processed and by determining the degree of processing of oligosaccharides on mature α-chains.