CD3complex

The CD3 complex is a multi-subunit signaling complex that associates with the T cell receptor (TCR) on the surface of T cells. It comprises invariant CD3 chains, including CD3 gamma, delta, and epsilon, along with the CD3 zeta chains. These subunits form the core of the TCR–CD3 complex, which together with the TCR recognizes peptide antigens presented by major histocompatibility complex (MHC) molecules.

The CD3 subunits contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic tails. When the TCR engages an antigen, Src-family kinases such as Lck phosphorylate ITAMs, creating docking sites for ZAP-70. Activated ZAP-70 then propagates signaling through downstream pathways, including calcium flux with calcineurin/NFAT, PKC/NF-κB, and MAPK cascades, driving T cell activation, proliferation, and differentiation.

The CD3 complex is essential for surface expression of the TCR and for effective signal transduction. It is expressed on mature T cells and thymic precursors, and defects in CD3 subunits can impair T cell development and cause immunodeficiency. As a surface marker, the complex is used in immunophenotyping to identify T cells in clinical samples.

Clinical relevance includes the use of anti-CD3 monoclonal antibodies, such as muromonab-CD3, to modulate T cell activity in transplantation and certain immunological settings. Genetic variation or altered expression of CD3 subunits can influence immune responses and susceptibility to disease.