Intracellular competition for component chains determines class II MHC cell surface phenotype

Abstract

Mixed isotype (E alpha A beta and A alpha E beta) dimers are not found on Ia+ hematopoietic cells, although some pairs (e.g., E alpha A beta d) reach the membrane of transfected cells expressing only the two relevant class II genes. To examine the basis for this difference in potential versus actual Ia molecule expression, we utilized an L cell transfection model more closely resembling the normal condition of multiple class II alpha and beta chain synthesis within a single cell, such that competition among alpha and beta chains could occur. The surface expression of individual Ia dimers was compared with the available class II chains in such cells. Our data indicate that 3- to 5-fold preferences in assembly or transport of the predominant A alpha A beta and E alpha E beta species preclude expression of the mixed isotype E alpha A beta pair under physiologic conditions of balanced chain synthesis, but that asymmetric chain synthesis can lead to the expression of such mixed dimers on the cell surface in biologically significant amounts.