STRUCTURAL MUTATIONS OF THE T-CELL RECEPTOR ZETA-CHAIN AND ITS ROLE IN T-CELL ACTIVATION

T cell hybridomas that express ζζ, but not ζη, dimers in their T cell receptors (TCRs) produce interleukin-2 (IL-2) and undergo an inhibition of spontaneous growth when activated by antigen, antibodies to the receptor, or antibodies to Thy-1. Hybridomas without ζ and η were reconstituted with mutated; chains. Cytoplasmic truncations of up to 40% of the ζ molecule reconstituted normal surface assembly of TCRs, but antigen-induced IL-2 secretion and growth inhibition were lost. In contrast, crosslinking antibodies to the TCR activated these cells. A point mutation conferred the same signaling phenotype as did the truncations and caused defective antigen-induced tyrosine kinase activation. Thus, ζ allows the binding of antigen/major histocompatibility complex (MHC) to ap to effect TCR signaling.