title: 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.
abstract: 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.
mesh_terms: D000483:Alleles; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000235:genetics; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000276:immunology*; D005802:Genes, MHC Class II; D005815:Genetic Code; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains