TCR-gamma delta cells in CD3 zeta-deficient mice contain Fc epsilon RI gamma in the receptor complex but are specifically unresponsive to antigen.
Unlike TCR-alpha beta cells, TCR-gamma delta cells express a distinct member of the zeta family, the gamma-chain of Fc epsilon RI (Fc epsilon RI gamma) within the TCR complex. To study the role of the Fc epsilon RI gamma-chain in TCR-gamma delta cells, a TCR-gamma delta transgenic mouse (G8) has been crossed with CD3 zeta-chain-deficient mice (G8.zeta-/-). Thy-1+ spleen and lymph node cells of these animals expressed low levels of CD3/TCR. These results suggested that the zeta-chain is required for effective TCR transport to the cell surface. In contrast, intraepithelial TCR-gamma delta cells of G8.zeta-/- mice expressed high levels of TCR. Immunoprecipitation with anti-CD3 showed that Fc epsilon RI gamma-chains were associated with the TCR complex in T cells isolated from zeta-deficient mice. Although the Fc epsilon RI gamma-expressing T cells proliferated in response to stimulation by TCR-specific Abs including anti-CD3 epsilon, anti-pan gamma delta, and anti-V gamma 2 mAb, the G8.zeta-/- T cells did not respond to the G8-specific Ag (T10b), anti-Thy-1 mAb, or Con A. The unresponsiveness to the Ag was not due to the reduced TCR expression, because intraepithelial TCR-gamma delta cells from the zeta-deficient mice did not respond to Ag. The inability of the G8.zeta-/- T cells to respond to Ag could not be overcome by providing an anti-CD28 costimulatory signal or by adding exogenous rIL-2. Taken together, our data suggest that the Fc epsilon RI gamma-chain associates with the TCR-gamma delta complex in the absence of the zeta-chain, but it is not able to substitute for the zeta-chain for effective transport of TCR to the cell surface or functional responses to Ag.
Khattri
R
R
Ben May Institute for Cancer Research, University of Chicago, IL 60637, USA.
Sperling
A I
AI
Qian
D
D
Fitch
F W
FW
Shores
E W
EW
Love
P E
PE
Bluestone
J A
JA
D000818:Animals; D018106:CD28 Antigens / Q000494:pharmacology; D000939:Epitopes / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics*; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000172:deficiency* / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D017455:Receptors, IgE / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D018106:CD28 Antigens; D000939:Epitopes; D007376:Interleukin-2; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017455:Receptors, IgE; C054979:antigen T cell receptor, zeta chain