CD3G Gene

CD3G (CD3G stands for "CD3gamma") is a protein-coding gene located on chromosome 11q23.3. The protein encoded by this gene is the CD3-gamma polypeptide, which together with CD3-epsilon, -delta, and -zeta and the T cell receptor alpha/beta and gamma/delta heterodimers forms the T cell receptor-CD3 complex. The T cell receptor-CD3 complex plays an important role in coupling antigen recognition to various intracellular signal transduction pathways.

The genes encoding the epsilon, gamma, and delta polypeptides are located in the same cluster on chromosome 11, and defects in this gene are associated with T cell immunodeficiency.

Diseases associated with CD3G include:

• Immunodeficiency 17 (OMIM: 615607; Arnaiz-Villena A et al. 1992)
• and
• Immunodeficiency 19 (OMIM:615617; Gil J et al 2011).

Associated signaling pathways include the phospholipase C pathway and the ICos-ICosL pathway in T helper cells.

The CD3gamma protein forms part of the TCR-CD3 complex on the surface of T lymphocytes. This plays an essential role in the adaptive immune response. Upon T cell receptor activation by antigen-presenting cells (APCs), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G, and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR binding, these motifs are phosphorylated by Src family protein tyrosine kinases LCK and FYN, leading to activation of downstream signaling pathways. In addition to this signal transduction role in T cell activation, CD3G plays an essential role in the dynamic regulation of TCR expression at the cell surface.

1. Arnaiz-Villena A et al (1992) Primary immunodeficiency caused by mutations in the gene encoding the CD3-gamma subunit of the T-lymphocyte receptor. New Eng J Med 327: 529-533.
2. Gil J et al (2011) A leaky mutation in CD3D differentially affects alpha-beta and gamma-delta T cells and leads to a T-alpha/beta-T-gamma/delta+B+NK+ human SCID. J Clin Invest 121: 3872-3876.
3. Perez-Aciego P et al (1991) Expression and function of a variant T cell receptor complex lacking CD3-gamma. J Exp Med 174: 319-326.