Family of disulphide-linked dimers containing the ζ and η chains of the T-cell receptor and the γ chain of Fc receptors

Abstract

STIMULATION of T cells by antigen activates many signalling pathways¹. The capacity for this range of biochemical responses may reside in the complex structure of the seven-chain T-cell antigen receptor (TCR)². In addition to the complexity shared by all TCRs, coexpression of zeta (ζ) and the distinct but related eta (η) chain creates structural diversity among the TCR complexes expressed on a given cell^3,4. In most murine T cells that we have studied, about 90% of the heptameric receptor complexes contain a ζζ disulphide homodimer, whereas 10% contain a ζη disulphide heterodimer⁵. Recent studies suggest that ζ has a critical role in allowing antigen to activate the cell, whereas η expression has been correlated with the capacity for antigen-induced phos-phoinositide turnover^6,7. A third ζ-related protein, the gamma (γ) chain of the Fee and some Fcγ receptors, exists as a disulphide homodimer in those complexes^8–10. The structural relatedness of ζ and γ is emphasized by the recent demonstration of ζζ in association with CD16 in TCR-negative natural killer cells^11–13. Here we identify T cells lacking Fc receptors but coexpressing ζ, γ and η, document the formation of novel heterodimers between ζ and γ and between η and γ and show their association with the TCR. A greater range of homologous coupling structures than previously thought may be one way of achieving the variety of TCR-mediated (and possibly Fc receptor-mediated) biochemical responses and effector functions.