EXPRESSION OF THE H2-EA GENE IS MODULATED BY A POLYMORPHIC TRANSCRIPTIONAL ENHANCER

In all vertebrates the major histocompatibility complex (MHC) class II genes are polymorphic in their coding regions as well as in their pro moter control elements. This polymorphism correlates with a variabilit y in peptide binding and a variability in transcriptional activities. There is, however, one exception to this rule, which is the mouse H2-E a gene or the corresponding human DRA gene. So far and for unkown reas ons no polymorphism has been observed in these loci. We sequenced the distal transcriptional control elements of the H2-Ea, H2-Eb, and H2-Ab genes from the mouse haplotypes H2(d), H2(k), H2(q), and H2(z), and i n contrast to the promoter and coding regions a sequence polymorphism can be detected which is limited to the H2-Ea gene. In transfection ex periments this polymorphism can be seen to influence haplotype-specifi cally the transcriptional activities in B cells. This finding strongly suggests an evolutionary pressure towards a haplotype-specific expres sion pattern in all four MHC class II genes. The genetic differences i n control elements of MHC class II genes may well contribute to differ ential immune reactivities and to immune disorders like allergies or a utoimmune diseases.