Unexpected expression of a unique mixed-isotype class II MHC molecule by transfected L-cells

Abstract

Class II (Ia) major histocompatibility complex (MHC) molecules are heterodimeric integral membrane proteins composed of non-covalently linked α and β glycoprotein chains^1,2. Studies of both normal cells and L-cell transfectants have shown that neither α-nor β-chains are found on the cell surface alone, and that αβ dimers are required for membrane expression^1-6. In both mouse and man, several distinct non-allelic α and β genes exist. Analysis of Ia molecules by immunoprecipitation and two-dimensional gel electrophoresis has demonstrated apparently selective association of particular pairs of the various α- and β-chains to form the expressed class II isotypes I–A and I–E (mouse) or DQ, DP and DR (human)¹. Because the various α- or β-chains encoded by distinct loci exist in many allelic forms within a species^1,2,7,8, such specific pairing suggests a special role for isotypically conserved regions of each chain in the association process. In attempting to localize such putative assembly-controlling regions using the technique of DNA-mediated gene transfer, various combinations of murine α and β genes were introduced into L-cells. Here we report the unexpected observation, following transfection, of mixed-isotype (A^d_βE^a/k_α) molecules on the L-cell membrane and document that the formation of this pair is strongly influenced by allelic polymorphism of the A_β chain.