Distinct Structure and Signaling Potential of the γδTCR Complex

Abstract

Alpha beta and gamma delta T cells are distinguished by the clonotypic subunits contained within their TCRs. Although the alpha beta TCR has been well characterized, much less is known about the gamma delta TCR. Here, we report that, unlike alpha beta T CRs, most gamma delta TCRs expressed on ex vivo gamma delta T cells lack CD3 delta. Despite this structural difference, signal transduction by the gamma delta TCR is superior to that of the alpha beta TCR, as measured by its ability to induce calcium mobilization, ERK activation, and cellular proliferation. Additionally, the TCR complexes expressed on primary gamma delta T cells contain only zeta zeta homodimers; however, following activation and expansion, Fc epsilon R1 gamma is expressed and is included in the gamma delta TCR complex. These results reveal fundamental differences in the primary structure and signaling potential of the alpha beta- and gamma delta TCR complexes.

Importance of the CD3γ Ectodomain Terminal β-Strand and Membrane Proximal Stalk in Thymic Development and Receptor Assembly

“…These data suggest that both pre-TCR and ␣␤ TCR functions are affected. Although we did not directly evaluate ␥␦ TCR-expressing cells, given that CD3 ␥ is the only heterodimer associated with this TCR (35), one would expect this lineage to be altered as well, consistent with findings in CD3␥ Ϫ/Ϫ mice noted previously (27,34).…”

Expansion of human γ/δ T cells in vitro is differentially regulated by the measles virus glycoproteins

“…1b and 2). Thus, although there is evidence that signalling properties of the c/d TCR complex are quite different, and even superior to those of the a/b TCR (Hayday, 2000;Hayes & Love, 2002), IPP/IL-2 stimulation does not rescue expansion of these cells. It is likely that, for MV-mediated inhibition of IPP/IL-2-stimulated c/d TCR T cells, similar mechanisms are operative as for those induced by mitogens or anti-CD3/ CD28 in PBMCs or purified T cell cultures.…”

FcRγ Presence in TCR Complex of Double-Negative T Cells Is Critical for Their Regulatory Function

“…Several other activating receptors, including the paired Ig-like receptor A (20), Ig-like transcript/leukocyte Ig-like receptor (CD85) (21), platelet glycoprotein VI (22), as well as the primary activating receptor on T cells, the TCR complex (23), also may contain FcR␥. Although relatively rare, FcR␥-containing TCR complexes have been found to be expressed in NK-like T cells (NKT) (24), activated TCR␥␦ ϩ T cells (25), human systemic lupus erythematosus (SLE) T cells (26), and some human effector CD4 ϩ T cells (27). Within the subset of T cells expressing FcR␥, it has been shown to take the place of the conventional CD3 by regulating the expression of TCR complexes at the cell surface and mediating signal transduction through ITAMs upon receptor engagement (28).…”