CD3D Gene

The CD3D (CD3d molecule) gene is a protein-coding gene located on chromosome 11q23.3. The protein encoded by this gene is part of the T cell receptor/CD3 complex (TCR/CD3 complex) and is involved in T cell development and signal transduction. The encoded membrane protein represents the delta subunit of the CD3 complex and binds with four other CD3 subunits to either TCR alpha/beta or TCR gamma/delta to form the TCR/CD3 complex on the surface of T cells.

Two transcript variants encoding different isoforms have been found for this gene to date.

Defects in this gene are a cause of:

• Immunodeficiency 19 (Autosomal recessive severe combined immunodeficiency T cell negative/B cell positive/NK cell positive; IMD19, OMIM: 615617).

and

• T-B+ Severe Combined Immunodeficiency due to Cd3delta/Cd3epsilon/Cd3zeta.

The encoded CD3d molecule is part of the TCR-CD3 complex on the cell surface of T lymphocytes, which plays an essential role in the adaptive immune response. 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 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 (PubMed:2470098). In addition to this signal transduction role in T cell activation, CD3D plays an essential role in thymocyte differentiation. Namely, it is involved in proper intracellular TCR-CD3 complex formation and surface expression. In the absence of a functional TCR-CD3 complex, thymocytes cannot differentiate properly. Interacts with CD4 and CD8, thus establishing a functional link between the TCR and the CD4 and CD8 coreceptors, which is required for the activation and positive selection of CD4 or CD8 T cells

1. Yu GP et al (2011) Genotype, phenotype, and outcomes of nine patients with T-B+NK+ SCID. Pediat. Transplant. 15: 733-741.