Mutants in signal transduction through the T-cell antigen receptor.

Abstract

Mutants of an untransformed helper T-cell clone have been derived by chemical mutagenesis followed by selection for cells incapable of proliferating in response to antigen or anti-CD3. The selection was designed to enrich cells bearing mutations distal to the T-cell antigen receptor. The mutants express normal levels of functional T-cell receptors but are uncoupled from cellular responses, including gene induction, lymphokine secretion, proliferation, and phosphatidylinositol turnover. Responses to phorbol ester plus calcium ionophore and to interleukin-2 are unimpaired. Responses to antigen were restored by fusion with a T-cell receptor-negative thymoma, making the mutants valuable for investigating the mechanisms that couple T-cell receptor stimulation to the induction of second messengers and subsequent physiologic responses.