Qualitatively distinct signaling through T cell antigen receptor subunits

T cell antigen receptors (TCR) contain several subunits including CD3γ, δ, and ϵ, and TCRζ and η which are capable of mediating signal transduction. It is unclear whether the signaling function of these subunits is completely redundant. To assess the relative signaling capabilities of TCR subunits, we compared proximal events in signal transduction by wild‐type TCR complexes and TCR devoid of functional ζ subunits, as well as chimeric receptors containing the cytoplasmic domains of TCRζ or CD3ϵ. Results demonstrate that in BW5147 wild‐type TCR, tail‐less ζ TCR, CD3ϵ, and TCRζ transduce signals leading to tyrosine phosphorylation of similar sets of cellular substrates, including the receptor subunits, Fyn, ZAP‐70, and phospholipase Cγ1 (PLCγ1). Surprisingly, unlike wild‐type TCR, tail‐less ζ TCR, and CD3ϵ, TCRζ was incapable of transducing signals resulting in inositol triphosphate (IP3) generation or intracellular free calcium ([Ca2+]i) mobilization. These data indicate that tyrosine phosphorylation of PLCγ1 is not sufficient to drive IP3 production and [Ca2+]i mobilization. Most importantly, data presented indicate that TCRζ and CD3ϵ engage partially distinct signaling pathways.