Specificity of antigen binding by T cells; competition between soluble and Ia-associated antigen

Competitive antigen binding experiments were performed with purified T and B cells of C3H.SW (H-2b) mice. As antigen, (T,G)-A--L [poly-L(Tyr,Glu)-poly-DL-ALa-poly-L Lys] was used, both in an Ia-containing form, released by adherent cells (IAC-Puri and Lonai, Eur. J. Immunol. 1980. 10:273), and in regular solution. It was found that regular (T,G)-A-L did not compete with the binding of 125I-labeled-IAC-(T,G)-A--L even at a 10(4)-fold excess, whereas IAC-(T,G)-A--L inhibited binding at 10-fold excess. The specificity of (T,G)-A--L binding to high-responder T and B cells was compared by using related branched synthetic copolymers as competitors. B cells cross-reacted with (T,G)-A--L, (H,G)-A--L, (G)-A--L and (T,G)-Pro--L. In contrast, antigen binding C3H.SW T cells cross-reacted only with (T,G)-A--L and (Phe, G)-A--L to both of which they are Ir gene-controlled high responders. Evidence for the Ir gene control of IAC-binding T cells was obtained by showing that high X low responder F1 hybrid T cells preferentally bind IAC-(T,G)-A--L processed by processor cells deriving from the high-responder parental strain. These data are interpreted to suggest that T cells have high affinity for antigen plus self Ia complexes, whereas they have a much lower, if any, affinity for free antigen. It also follows from the results that the structure of the complex ligand may have a role in defining the specificity, H-2 restriction and Ir gene control of T cells.