T-cell surface glycoprotein CD3 epsilon chain (CD3E) on gamma-delta T cells (CD3E)

The T-cell receptor (TCR) complex on gamma-delta (γδ) T cells is a specialized molecular assembly responsible for recognizing non-peptide antigens, such as phosphoantigens and stress-induced molecules (Silva-Santos et al., 2019). The CD3 epsilon (CD3E) chain is a vital component of this complex, forming heterodimers with CD3 gamma or CD3 delta to facilitate the assembly and surface expression of the TCR (UniProt P07766). Upon antigen binding, CD3E mediates signal transduction through its cytoplasmic immunoreceptor tyrosine-based activation motifs (ITAMs), triggering T-cell proliferation and the release of cytotoxic granules (Call & Wucherpfennig, 2005). In the context of immunotherapy, CD3E on γδ T cells is a primary target for bispecific T-cell engagers (BiTEs) and other multispecific antibodies designed to recruit these cells to tumor sites. These therapies aim to bridge γδ T cells with tumor-associated antigens, bypassing traditional MHC restriction to induce potent anti-tumor activity (LAVA Therapeutics, 2023). While γδ T cells are less abundant than alpha-beta T cells, their unique ability to infiltrate solid tumors and their lower propensity for causing graft-versus-host disease make the γδ TCR-CD3 complex an attractive target for next-generation cancer treatments.

Other names

CD3 epsilonCD3eT-cell receptor-CD3 complexgamma-delta TCR-CD3 complexT3ECD3E on gamma-delta T cells

Bispecific T-cell engagement and redirected cytotoxicity