Functional expression of a microinjected Edα gene in C57BL/6 transgenic mice

Abstract

The class II major histocompatibility antigens, I–A and I–E, have been detected on the surface of certain immunocompetent cells, including B lymphocytes and monocytes^1–3. These molecules are involved in cell–cell interactions in the immune responses^4,5. Each class II antigen consists of two subunits, α and β chains, and the genes encoding these subunits have been well characterized at the molecular level^6–9. To analyse the regulatory mechanism of Eα gene expression and the role of the I–E antigen in the regulation of the immune responses, we have produced transgenic mice by microinjecting cloned E^d_α genes into fertilized eggs of C57BL/6 mice of b haplotype. This strain of mouse carries a deletion in the upstream (5′) region of the Eα gene covering the transcriptional promoter and, therefore, does not express this gene¹⁰. Interestingly, this genetic defect of the Eα gene is accompanied by the inability of the host mouse to respond to a certain set of antigens, phenomena generally termed Ir gene control^11,12. We report here that the E^d_α genes are expressed in these transgenic mice to form the I–E^d_αE^d_β antigen on the surface of B lymphocytes and monocytes and that these I–E antigens are functional in terms of the induction of a mixed lymphocyte reaction and the restoration of immune responsiveness to poly(L-glutamic acid-L-lysine-L-phenylalanine) (GL-Phe).