Differential signal transduction via T-cell receptor CD3ζ₂, CD3ζ-η, and CD3η₂ isoforms

The T-cell antigen receptor (TCR) consists of an antigen-binding heterodimer, termed Ti, which is noncovalently associated with the invariant CD3 subunits (γ, δ, ε, ζ, and η). The CD3ζ and -η subunits form either homodimeric or heterodimeric structures in turn associated with the other components of the TCR complex. This feature increases the structural complexity of TCRs by creating "isoforms." Both CD3ζ and -η are thought to play an important role in signal transduction triggered by antigen/major histocompatibility complex. To compare signaling functions of TCR isoforms, MA5.8, a CD3ζ^-η^- variant of the cytochrome c-specific, I-E^k-restricted T-cell hybridoma 2B4.11, was stably transfected with cDNAs encoding CD3ζ and/or CD3η, and resulting clones were characterized. The findings indicate that signals inducing Ca²⁺ mobilization, phosphatidylinositol turnover, and interleukin 2 production are each transmitted by the above TCR isoforms. In contrast, tyrosine phosphorylation of the CD3ζ subunit but not the CD3η subunit follows TCR stimulation. Given the general importance of tyrosine phosphorylation for receptor signaling, it is likely that this difference between TCR isoforms plays a regulatory role in T-lineage function by qualitatively or quantitatively altering signaling events.