Role of beta2-microglobulin in the intracellular processing of HLA antigens.
The biosynthesis of HLA-A, -B, and -C antigens was examined in the two lymphoblastoid cell lines DAUDI and RAJI. In RAJI cells the HLA-A, -B, and -C antigen heavy chains become core-glycosylated in the endoplasmic reticulum as evidenced by their sensitivity to endo-H digestion and tunicamycin treatment. Beta2-Microglobulin is present in excess in the endoplasmic reticulum of the RAJI cells and associates with the heavy chain at the time of synthesis of the heavy chain. Pulse-chase experiments demonstrated that the RAJI HLA-A, -B, and -C antigen heavy chains become terminally glycosylated since their changed characteristics included resistance to endo-H digestion, sensitivity to neuraminidase treatment, and incorporation fucose. DAUDI HLA-A, -B, and -C antigen heavy chains are synthesized normally and become core-glycosylated but not terminally glycosylated. Other glycosylated cell surface proteins, like the HLA-DR antigens, display normal glycosylation in DAUDI cells. Therefore it is unlikely that the absence of terminally glycosylated HLA-A, -B, and -C antigen heavy chains is the result of a general defect in the biosynthetic machinery of DAUDI cells. However, DAUDI cells lack the ability to synthesize beta2-microglobulin, the common subunit of all HLA-A, -B, and -C antigens. Therefore, it seems reasonable to conclude that beta2-microglobulin is of importance for intracellular transport of newly synthesized HLA-A, -B, and -C antigens.
D001609:Beta-Globulins / Q000276:immunology*; D002460:Cell Line; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D007945:Leukemia, Lymphoid; D008214:Lymphocytes; D008970:Molecular Weight; D014415:Tunicamycin / Q000494:pharmacology; D001613:beta 2-Microglobulin / Q000276:immunology*
D001609:Beta-Globulins; D006680:HLA Antigens; D001613:beta 2-Microglobulin; D014415:Tunicamycin