Interaction between I region loci influences the expression of a cell surface Ia antigen

Loci clustered in the I region of the murine H-2 gene complex control the capacity to generate an immune response against foreign antigens (Ir loci) and control differentiation antigens which appear to serve as structures used by cells to interact with and regulate one another (Ia loci). Both genetic and functional studies suggest that Ia antigens may be products of Ir loci. Recent studies have shown that interaction between closely linked Ir loci is required for generating immune responses to certain foreign antigens, and that interaction between H-2-linked loci determines the appearance of an Ia glycoprotein (the Ae chain) on lymphocyte cell surfaces. In this report, we show that one Ia locus regulates the quantitative expression of the product (the E alpha chain) of a second Ia locus. This regulatory locus is dominantly expressed and exerts its effects in either the cis or trans chromosomal position. Thus, the quantitative as well as the qualitative expression of some Ia products is dependent on interaction between tightly linked loci. Our results suggest a possible molecular basis for this regulation: the synthesis and intracellular association of Ae and E alpha chains may be an absolute requirement for the expression of normal levels of either polypeptide chain on the lymphocyte cell surface. The implications these findings have for I region control of immune responses and study of human HLA-D antigens are discussed.