Analysis of T cell responses to poly-L(GluLys) at the clonal level. I. Presence of responsive clones in nonresponder mice

The synthetic random copolymer of L-glutamic acid and L-lysine (GL) is weakly or nonimmunogenic in all inbred strains of mice. Theories proposed to account for nonresponsiveness to GL include a deficient T cell repertoire, failure of antigenpresenting cells to present the antigen and/or the presence of suppressor cells. In this study we examine mechanisms for nonresponsiveness to GL. We demonstrate the existence of GL-reactive T cells which can be isolated with a relatively high frequency. These clones, which were derived following immunization of H-2^d mice with poly(LGluLLysLTyr), also respond to several GL-containing polypeptides including the terpolymers of GL with phenylalanine, alanine (GLA) or leucine. Although recognition of GLA by heterogeneous T cell populations usually occurs in association with I-A determinants, these clones recognize GLA, as well as the other GL-containing polymers, in association with I-E determinants. Analysis of the antigen and alloreactivity patterns of these clones indicated that they expressed distinct antigen receptors. These studies imply that the T cell repertoire of “nonresponder” H-2^d mice includes multiple GL-reactive T cell clones and that the antigen-presenting cells of these mice are effective in processing and presenting GL.