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

Alternate Names

delta polypeptide, T3D, TiT3

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TRG

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Product Specific Notices for TCR gamma/delta Antibody (11F2) [Alexa Fluor® 488]

Alexa Fluor (R) products are provided under an intellectual property license from Life Technologies Corporation. The purchase of this product conveys to the buyer the non-transferable right to use the purchased product and components of the product only in research conducted by the buyer (whether the buyer is an academic or for-profit entity). The sale of this product is expressly conditioned on the buyer not using the product or its components, or any materials made using the product or its components, in any activity to generate revenue, which may include, but is not limited to use of the product or its components: (i) in manufacturing; (ii) to provide a service, information, or data in return for payment; (iii) for therapeutic, diagnostic or prophylactic purposes; or (iv) for resale, regardless of whether they are resold for use in research. For information on purchasing a license to this product for purposes other than as described above, contact Life Technologies Corporation, 5791 Van Allen Way, Carlsbad, CA 92008 USA or outlicensing@lifetech.com. This conjugate is made on demand. Actual recovery may vary from the stated volume of this product. The volume will be greater than or equal to the unit size stated on the datasheet.

This product is for research use only and is not approved for use in humans or in clinical diagnosis. Primary Antibodies are guaranteed for 1 year from date of receipt.

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TCR gamma/delta Antibody (11F2) [Alexa Fluor® 488]

Novus Biologicals, part of Bio-Techne | Catalog # NBP3-14621AF488

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Background: TCR gamma/delta