Reconstitution of Ir genes, Ia antigens, and mixed lymphocyte reaction determinants by gene complementation.

By using clones of murine T cells reactive with alloantigens as well as soluble antigens, it has been possible to demonstrate that Ia antigens, Ir gene phenomena (defined as the ability of immune T cells to recognize antigen), and mixed lymphocyte reaction (MLR)-stimulating determinants encoded within the I-A subregion are different manifestations associated with same product. These studies utilized the I-Ab mutant mouse B6.C-H-2bm (bm12), whose defect in the normal expression of the cell surface products of the I-Ab subregion can be partially circumvented through trans-complementation by deriving hybrids between bm12 and mice expressing normal I-A subregion products. Such mice [e.g., (bm12 X B10.A)F1] express several serologically normal I-Ab products but have defects in certain I-A subregion gene products normally expressed on cells of H-2a X H-2b heterozygote mice that are used as restricting elements for antigen recognition by antigen-reactive T cell clones or recognized as alloantigens by alloreactive T cell clones. This defect in cell surface expression of certain normal I-Ab products on the mutant bm12 cells has allowed us to suggest that there exist trans-complementing products on H-2a X H-2b heterozygote mice consisting of Ab alpha Ak beta and Ak alpha Ab beta that restrict antigen recognition by cloned T cells, stimulate MLR responses by cloned T cells, and react with certain anti-Ia antisera.