ASSEMBLY AND INTRACELLULAR-TRANSPORT OF HLA-DM AND CORRECTION OF THE CLASS-II ANTIGEN-PROCESSING DEFECT IN T2 CELLS

MHC class II molecules expressed in T2 cells fail to acquire a normal complement of endocytically generated peptides. The defect is repaired by introducing HLA DMA and HLA DMB cDNA expression vectors, determined by the restoration of SDS stability of class II alpha beta dimers, restoration of a normal conformation for HLA-DR3 as detected by a monoclonal antibody, and by a reduction in class II-associated invariant chain peptides. The intracellular distribution of class II and invariant chain molecules is also restored to that of wild-type cells. The HLA DMA and HLA-DMB products appear to form a heterodimer that, although transported at least to the medial Golgi, is not expressed at the cell surface. These findings are consistent with HLA-DM functioning intracellularly to facilitate class II-restricted antigen processing.