I-region genetic restrictions imposed upon the recognition of KLH by murine T-cell clones.

Data presented in this paper show that the recognition of keyhole limpet hemocyanin by murine T-cell clones is restricted by products of the I region. These data have been obtained by genetic mapping studies as well as by the use of monoclonal Ia-specific antibodies which inhibit the ability of antigen-presenting cells to effectively present antigen to such T- cell clones. Use of heterozygous antigen-presenting cells derived from crosses between B6.C-H-2bm12 and B10.A(4R) mice have allowed us to show that both trans-complementing I-A products are used for restriction of recognition of KLH. These data were confirmed using monoclonal Ia antibodies to inhibition recognition of KLH by the same T -cell clones. Thus, we have shown that there exist hybrid molecules formed by free combinatorial association of products encoded within the I-A subregion which restrict the recognition of soluble antigen. Additionally, we have shown that the molecule formed by complementation between the alpha chain encoded within the I-E region and a beta chain encoded within the A region (Ae) can fuction effectively in presenting KLH to certain murine T -cell clones. These results support the hypothesis that the recognition of individual antigenic epitopes within large multideterminant antigens is under the control of Ir genes.