BETA(2)-MICROGLOBULIN INDUCES A CONFORMATIONAL CHANGE IN AN MHC CLASS-I H-CHAIN THAT OCCURS INTRACELLULARLY AND IS MAINTAINED AT THE CELL-SURFACE

beta(2)-microglobulin (beta(2)-m) can regulate the cell surface conformation and expression of a class I MHC H chain. To further determine how the intracellular association of beta(2)-m with a class I H chain influences the subsequent cell surface conformation and expression of the H chain, we examined the expression of HLA-A3 H chains in transgenic mice. We found that the overall conformation and level of expression of a transgenic HLA-A3 H chain is determined by its previous intracellular association with beta(2)-m during its maturation in the endoplasmic reticulum, and that this conformation is not altered appreciably after the H chain reaches the cell surface. This conclusion is based on two observations. First, the conformation-dependent W6/32 mAb reacts with an HLA-A3 H chain bound to human beta(2)-m (h beta(2)-m) on the surface of lymphocytes from (A3 x h beta(2)-m)F-1 double transgenic mice in which the two chains associate intracellularly after synthesis and are then co-transported to the surface membrane. Second, this W6/32 mAb does not react with an HLA-A3 H chain/h beta(2)-m surface complex formed by the exchange of H chain bound mouse beta(2)-m for exogenously added h beta(2)-m on lymphocytes from A3 single transgenic mice in which the HLA-A3 H chain is synthesized and transported to the cell surface in association with mouse beta(2)-m.