KLH-specific, I-E/C-restricted clones of proliferating T lymphocytes

The recognition of keyhole limpet hemocyanin by a substantial proportion of proliferating clones of murine T lymphocytes was found to be restricted by the I-E/Ck molecule, which is a combinatorial product of genes located in the I-A (Ae) and I-E/C (E alpha) subregions of the murine major histocompatibility complex. The respective roles of the Ae (polymorphic) and E alpha (oligomorphic) gene products in the expression of the structures which are used as restriction elements by these T-cell clones was analyzed by mating parental strains unable to present the antigen and bearing selected Ae and E alpha alleles. Efficient complementation for antigen presentation was found to require the expression by accessory cells of the Aek-gene product, whereas all E alpha allelic molecules were functionally equivalent. These results (a) indicate that the immunoregulatory role of I-region gene products, initially described for molecules selected for their limited number of antigenic epitopes, also applies to complex multiepitopic antigens; (b) illustrate the advantage which results from the diversity of the Ia molecules expressed by accessory cells for the development of potent immune responses; and (c) suggest that a correlation might exist between the degree of polymorphism of a given family of H-2 allelic molecules and their ability to be used as restriction elements for antigen recognition by T lymphocytes.