The T cell response to allelic determinants on Igh-1-encoded IgG2a antibodies: dual recognition examined by using antigenic antibodies with binding affinity for Ia molecules.

In this report we examine the effects of binding antigen directly to Ia molecules during immunization and stimulation of T cells in culture. To accomplish this we characterize the T cell response to Igh-1j-encoded IgG2a antibodies in C57BL/10 H-2 congenic mice. In contrast to the response to the closely related Igh-1a-encoded IgG2a antibodies, high responder mice were (C57BL/10 X B10.A)F1 hybrids, and the important alleles appeared to map to I-Ab and I-Ak. C57BL/10 and B10.A(5R) strains were low responders (I-Ab), and B10.A and B10.A(4R) strains were nonresponders (I-Ak). The interest in using monoclonal IgG2a antibodies as T cell antigens was that different V-region-encoded binding specificities could be associated with the same IgG2a antigenic determinant. In our interpretation of the Langman and Cohn dual binding site model of the T cell receptor, the response to anti-Ia antibody should have some of the same characteristics as that to an allogeneic Ia molecule; in particular, it should be non-H-2-restricted. Although the response to anti-Ia antibody had several interesting properties, no difference in the restriction specificity was found for the T cell response to anti-Ia antibodies relative to unreactive IgG2a antibodies. Our conclusion is that T cell receptors must bind both Ia and antigen molecules for activation to occur. In a separate set of experiments, the T cell response resulting from immunization with anti-Ia antibody was examined. Because the antigen was shown to be associated with the Ia molecule during immunization, experiments were designed to detect an alteration or lack of H-2 restriction in the resulting T cell population. A long-term T cell line induced after such immunization showed no qualitative differences from a T cell line produced with unreactive IgG2a antibody. These results demonstrate that simply attaching a foreign antigen to a restriction element is not sufficient to lead to unrestricted T cell activation. This in turn suggests the T cell receptor must recognize the restriction element for cell-cell interactions to occur.