TCR gamma/delta Products

Description

T cell Receptor (TCR) gamma delta belongs to the immunoglobulin (Ig) superfamily and is a heterodimer consisting of a TCR gamma and a TCR delta chain (1). TCR gamma delta is expressed on the plasma membrane of T cells and is involved in ligand-induced signaling and tumor cell killing (1). While TCR gamma delta has structural similarity to TCR alpha beta, each receptor is expressed on unique T cell lineages and have different mechanisms of ligand recognition (1,2). The TCR gamma and delta chains have a variable region and constant region (1). The variable region contains complementary determining regions (CDRs) that form the antigen binding site whereas the constant region contains an Ig-like domain, a connecting peptide, a transmembrane region, and a cytoplasmic tail (1). TCR gamma delta T cells signal through the canonical T cell signaling complex, cluster of differentiation 3 (CD3), to help mediate T cell activation (1).

In humans, T cells expressing TCR gamma delta represents ~1-5% of total T cells in the peripheral blood but can comprise up to 50% of lymphoid cells in peripheral tissues like the intestines or dermis (3). The TCR gamma delta lineage arises from the double negative 3 (DN3) (CD44-,CD25-) stage of development where the cells receive strong TCR signals for gamma/delta selection (2). In contrast to alpha/beta T cells which are CD4+/CD8+, most gamma delta T cells are CD4-/CD8- (2). Gamma delta T cells produce different cytokines in response to varying degrees of signal received through the gamma delta TCR: a weaker signal induces interleukin (IL)-17, a moderate signal induces interferon (IFN)-gamma, and a strong signal stimulates IL-4 production (2,4). There are multiple gamma delta T cell subsets which are defined by the variable segments of the gamma and delta chain present after gene rearrangement (1,3,5). For example, Vgamma9Vdelta2 (Vgamma9Vdelta2) TCRs are expressed on the main subset of gamma delta T cells in human blood (1,3,5). Human gamma delta T cells expressing Vgamma9Vdelta2 TCR recognizes phosphoantigens that are released by tumor cells (3). The phosphoantigens bind butyrophilin (BTN) family members, such as BTN3A1/CD277, that are expressed on tumor cells and this interaction helps stimulate gamma delta T cell activation and tumor recognition (3). Considering their role in tumor recognition and killing, gamma delta T cells and the TCRs may be leveraged for cancer immunotherapies (3,4,6). Strategies for utilizing gamma delta T cells in immunotherapy include chimeric antigen receptor (CAR) transduction in gamma delta T cells, in vivo activation of gamma delta cells with anti-BTN3A1 monoclonal antibodies, or bispecific gamma delta T cell engagers (6).

References

1. Morath, A., & Schamel, W. W. (2020). AB and GD T cell receptors: similar but different. Journal of Leukocyte Biology, 107(6), 1045-1055. https://doi.org/10.1002/JLB.2MR1219-233R

2. Zarin, P., Chen, E. L., In, T. S., Anderson, M. K., & Zuniga-Pflucker, J. C. (2015). Gamma delta T-cell differentiation and effector function programming, TCR signal strength, when and how much?. Cellular Immunology, 296(1), 70-75. https://doi.org/10.1016/j.cellimm.2015.03.007

3. Silva-Santos, B., Serre, K., & Norell, H. (2015). GD T cells in cancer. Nature Reviews. Immunology, 15(11), 683-691. https://doi.org/10.1038/nri3904

4. Hahn, A. M., & Winkler, T. H. (2020). Resolving the mystery-How TCR transgenic mouse models shed light on the elusive case of gamma delta T cells. Journal of Leukocyte Biology, 107(6), 993-1007. https://doi.org/10.1002/JLB.1MR0120-237R

5. Fichtner, A. S., Ravens, S., & Prinz, I. (2020). Human GD TCR repertoires in health and disease. Cells, 9(4), 800. https://doi.org/10.3390/cells9040800

6. Kabelitz, D., Serrano, R., Kouakanou, L., Peters, C., & Kalyan, S. (2020). Cancer immunotherapy with gammadelta T cells: many paths ahead of us. Cellular & Molecular Immunology, 17(9), 925-939. https://doi.org/10.1038/s41423-020-0504-x

Bioinformatics

Entrez	110066 Mouse 110067 Mouse 24821 Rat 252921 Rat
Product By Gene ID	6965
Alternate Names	T cell receptor gamma locus T-cell antigen receptor, gamma polypeptide T-cell rearranging gene, gamma T-cell receptor, gamma cluster TCRG TRG