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/C^k molecule, which is a combinatorial product of genes located in the I-A (Ae) and I-EIC (E) subregions of the murine major histocompatibility complex. The respective roles of the Ae (polymorphic) and E (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 alleles. Efficient complementation for antigen presentation was found to require the expression by accessory cells of the Ae^k-gene product, whereas all E 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 la 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.Abbreviations used in this paper FCS fetal calf serum - Hepes N-2-hydroxypiperazine-N-2 ethanesulfonic acid; in polypeptides - G glutamate - L lysine - Ø phenylalanine - KLH keyhole limpet hemocyanin - m. Ab. monoclonal antibodies - T cells thymus-derived cells