Beta 2-microglobulin induces a conformational change in an MHC class I H chain that occurs intracellularly and is maintained at the cell surface.

Abstract

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)F1 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.