AN ESSENTIAL ROLE FOR HLA-DM IN ANTIGEN PRESENTATION BY CLASS-II MAJOR HISTOCOMPATIBILITY MOLECULES

IN antigen-presenting cells, class II molecules of the major histocomp atibility complex (MHC) bind peptides derived from endocytosed protein s1. In certain B-lymphoblastoid cell mutants, MHC class II molecule-pe ptide complex formation is impaired, resulting in deficient antigen-pr esenting function2. MHC deletion mutants with this defect map the resp onsible gene(s) to the class II region of the MHC3-5. Here we report t hat multiple independent mutants with the class II presentation defect harbour lesions in HLA-DMB, an MHC-linked gene encoding a class II-li ke beta-chain6,7. Expression of DMB complementary DNA in mutants lacki ng DMB messenger RNA restores the wild-type phenotype. These results e stablish HLA-DM as a critical regulatory molecule in class II-restrict ed antigen presentation and suggest that it functions at an intracellu lar site to promote class II molecule-peptide association.