CD3E Gene

CD3E (CD3e molecule) is a protein-coding gene located on chromosome 11q23.3. It is part of the TCR-CD3 complex on the surface of T lymphocytes, which plays an essential role in the adaptive immune response.

The protein encoded by this gene is the CD3 epsilon polypeptide, which together with CD3 gamma, delta, and zeta and the heterodimers of the T cell receptor alpha/beta and gamma/delta form the T cell receptor-CD3 complex. This 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 the epsilon polypeptide plays an essential role in T cell development. Defects in this gene lead to immunodeficiencies.

When antigen-presenting cells (APCs) activate the T cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G, and CD3Z. All CD3 protein 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, the CD3E protein plays an essential role in proper T cell development. It initiates the assembly of the TCR-CD3 receptor complex by forming the two heterodimers CD3D/CD3E and CD3G/CD3E. Furthermore, it is also involved in the internalization and down-regulation of the TCR-CD3 complexes on the cell surface via endocytosis sequences in the cytosolic region of CD3E

Diseases associated with CD3E include immunodeficiency 18 syndrome (T-B+ Severe Combined Immunodeficiency Due To Cd3delta/Cd3epsilon/Cd3zeta).

Furthermore, this gene has also been associated with susceptibility to type I diabetes in women.

1. Le Deist F et al (1991) Immunodeficiency with low expression of the T cell receptor/CD3 complex: effect on T lymphocyte activation. Europ J Immun 21: 1641-1647.
2. Liu Y et al.(2021) CXCL12 and CD3E as Indicators for Tumor Microenvironment Modulation in Bladder Cancer and Their Correlations With Immune Infiltration and Molecular Subtypes. Front Oncol 11:636870.
3. Natkunam Y et al (2018) Immunodeficiency-associated lymphoproliferative disorders: time for reappraisal? Blood 132:1871-1878.