Influence of allelic polymorphism on the assembly and surface expression of class II MHC (Ia) molecules

Abstract

Cell surface Ia expression was examined following transfection of murine alpha and beta class II major histocompatibility complex (MHC) genes into L cells. Although haplotype-matched (e.g., Ak beta Ak alpha) gene pairs yielded high expression in primary transfectants, haplotype-mismatched pairs (e.g., Ak beta Ad alpha) gave unexpectedly low expression. RNA analysis revealed a requirement for greater A beta, and particularly A alpha transcript levels in haplotype-mismatched vs. haplotype-matched transfectants with similar levels of membrane Ia. A beta allelic control of this assembly/expression process was mapped to the NH2-terminal (beta 1) domain, the locus of high intraspecies polymorphism. These data on the effects of allelic variation on Ia levels provide a possible explanation for the strong linkage disequilibrium of A alpha and A beta genes and may account for the current molecular organization of the I region of the MHC.