Molecular specificity of a monoclonal anti‐I^k alloantibody identifying a highly conserved determinant on mouse I‐A, I‐E and human DR antigens

We have investigated, using serological and biochemical assays, the specificity of an A.TH anti‐A.TL‐derived monoclonal antibody (mAb), designated 40.B, directed at a highly conserved antigenic determinant expressed on the majority of murine and human MHC class II antigens. In the mouse, mAb 40.B defines a new specificity expressed on the Ia products of the H‐2 haplotypes k, d, b, v, r, p, u, j and w3. Analysis of its reactivity with H‐2 recombinant strains and the results of the competitive binding inhibition of ¹²⁵I‐labeled mAb 40.B to B10.BR cells with I‐A^k and I‐E^k specific mAb suggested recognition of a shared Ia determinant expressed on both I‐A^k and I‐E^k molecules. This has been confirmed by sequential immunoprecipitation studies which demonstrated the specificity of mAb 40.B for the A_β^k A_α^k, A_β^b A_α^b, A_β^d A_α^d, E_β^k E_α^k, E_β^s E_β^k, and E_β^d E_α^d dimers. In humans, this mAb bound to and immunoprecipitated HLA‐D/DR molecules expressed on lymphoblastoid cell lines carrying the MTl and MT2 supertypic specificities. The possible implications of these findings with regard to an evolutionary model of MHC class II antigens are discussed.