CD3 Antibody (OKT3) [Janelia Fluor® 646]

Sold under license from the Howard Hughes Medical Institute, Janelia Research Campus.

CD3 (cluster of differentiation marker 3) is a multi-subunit transmembrane protein that is expressed on the surface of T-cells and forms a complex with the T-cell receptor (TCR) (1-3). CD3 consists of four distinct membrane protein isoforms: CD3-delta (delta), CD3-epsilon (epsilon), CD3-gamma, and CD3-zeta (1-3). The CD3 subunits organize into a complex containing three sets of dimers: CD3-epsilondelta, CD3-epsilongamma, CD3-zetazeta. The CD3 complex binds to the TCR heterodimer (alphabeta or gammadelta) to form the transmembrane TCR-CD3 complex (2-3). Structurally, the CD3 protein chains have an extracellular region, a transmembrane domain, and a cytoplasmic trail region (2-3). The CD3-epsilondelta and CD3-epsilongamma heterodimers also contain an extracellular immunoglobulin (Ig)-like domain, classifying them as part of the immunoglobulin superfamily (2-3). The cytoplasmic tail of each CD3 chain also contains one (delta, epsilon, gamma) or three (zeta) immunoreceptor tyrosine-based activation motifs (ITAMs), for a total of 10 ITAMs in the whole CD3 complex (2-3). Following, TCR binding to peptide major histocompatibility complex (p-MHC), the CD3 ITAMs are phosphorylated by the Src kinase Lck and are important for recruiting ZAP70 and initiating TCR signaling cascade activation (2). While similar in structure, the CD3 chains vary in length and molecular weight (4). The CD3-delta is 171 amino acids (aa) in length with a theoretical molecular weight of 18.9 kDa (4, 5). The CD3-epsilon is 204 aa long and has a theoretical molecular weight of 23 kDa (4, 5). CD3-gamma is 182 aa long with a theoretical molecular weight of 20.4 kDa (4, 5). Finally, CD3-zeta is 164 aa in length with a theoretical molecular weight of 18.6 kDa (4, 5).

CD3 proteins are expressed on the surface of thymocytes during thymocyte development, proliferation, and maturation to T-cells (4, 6, 7). During T-cell development CD4-CD8- double negative (DN) cells differentiate to CD4+CD8+ double positive (DP) cells before progressing to single positive (SP) CD4+ helper T-cells or CD8+ cytotoxic T-cells (4, 6, 7). As CD3 plays an important role in thymocyte development, it is understandable that CD3 defects and mutations in CD3 protein chains cause severe combined immunodeficiencies (SCIDs) (8). Additionally, a subset of CD3+ T-cells that co-express CD20 are described in a variety of diseases including rheumatoid arthritis, multiple sclerosis, CD20+ T-cell leukemia/lymphoma, and HIV (9). Clinical trials and animal models have shown that anti-CD3 monoclonal antibodies are a promising treatment modality for inflammatory disorders and autoimmune diseases, such as type I diabetes (10).

References

1. Chetty, R., & Gatter, K. (1994). CD3: structure, function, and role of immunostaining in clinical practice. The Journal of pathology. https://doi.org/10.1002/path.1711730404

2. Mariuzza, R. A., Agnihotri, P., & Orban, J. (2020). The structural basis of T-cell receptor (TCR) activation: An enduring enigma. The Journal of biological chemistry. https://doi.org/10.1074/jbc.REV119.009411

3. Kuhns, M. S., Davis, M. M., & Garcia, K. C. (2006). Deconstructing the form and function of the TCR/CD3 complex. Immunity. https://doi.org/10.1016/j.immuni.2006.01.006

4. Clevers, H., Alarcon, B., Wileman, T., & Terhorst, C. (1988). The T cell receptor/CD3 complex: a dynamic protein ensemble. Annual review of immunology. https://doi.org/10.1146/annurev.iy.06.040188.003213

5. Uniprot: CD3-delta (P04234), CD3-epsilon (P07766), CD3-gamma (P09693), CD3-zeta (P20963)

6. D'Acquisto, F., & Crompton, T. (2011). CD3+CD4-CD8- (double negative) T cells: saviours or villains of the immune response?. Biochemical pharmacology. https://doi.org/10.1016/j.bcp.2011.05.019

7. Dave V. P. (2009). Hierarchical role of CD3 chains in thymocyte development. Immunological reviews. https://doi.org/10.1111/j.1600-065X.2009.00835.x

8. Fischer, A., de Saint Basile, G., & Le Deist, F. (2005). CD3 deficiencies. Current opinion in allergy and clinical immunology. https://doi.org/10.1097/01.all.0000191886.12645.79

9. Chen, Q., Yuan, S., Sun, H., & Peng, L. (2019). CD3+CD20+ T cells and their roles in human diseases. Human immunology. https://doi.org/10.1016/j.humimm.2019.01.001

10. Kuhn, C., & Weiner, H. L. (2016). Therapeutic anti-CD3 monoclonal antibodies: from bench to bedside. Immunotherapy. https://doi.org/10.2217/imt-2016-0049

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.

Array NBP2-24867JF646

• CD3 Antibodies
• CD3 ELISA Kits