Author: V. Dimov, M.D.
Reviewer: S. Randhawa, M.D.

T-cell receptor complex

The TCR complex consists of the TCR, CD3 and two zeta (ξ) chains. CD3 has three distinct chains (γ, δ, and ε). CD3 is not found on NK cells. CD3 defect causes T-B+ SCID, it is one of the multiple causes of SCID.

CD3 is the signaling component of the T cell receptor (TCR) complex, present on all T-lymphocytes.

This video describes the cellular signaling that takes place with the T cell receptor. This video is from: Janeway's Immunobiology, 7th Edition Murphy, Travers, & Walport. Source: Garland Science.

T-cell receptor complex with TCR-α and TCR-β chains. Image source: Wikipedia.

CD3 is composed of three distinct chains (γ, δ, and ε) but it consists of 4 chains in total:

- CD3γ chain
- CD3δ chain
- two CD3ε chains

These chains associate with the T cell receptor (TCR) and the ζ-chain to generate an activation signal in T lymphocytes.

The TCR, ζ-chain (zeta-chain) and CD3 molecules together comprise the TCR complex.

The CD3γ, CD3δ, and CD3ε chains are of the immunoglobulin superfamily containing a single extracellular immunoglobulin domain.

The transmembrane region of the CD3 chains is negatively charged, and this allows them to associate with the positively charged TCR chains (TCRα and TCRβ).

The intracellular tails of the CD3 molecules contain a single immunoreceptor tyrosine-based activation motif (ITAM), which is essential for the signaling capacity of the TCR.

The first event following the TCR ligation (binding) is the activation of Src kinases - autoinhibitory loop.

CD45 phosphorylation in TCR signaling is of early and key importance. CD45 and ZAP70 defects cause SCID.


3 chains - a member of Ig superfamily


ZAP 70 binds to the Zeta chain (CD247) of the T-cell receptor.

Zeta-chain-associated protein kinase 70 (70 is the molecular weight in kDa)

ZAP70 deficiency is a form of SCID (T-/B+/NK+), one of the few SCID forms with palpable LN. ZAP-70 deficiency is a form of SCID with no CD8 cells and no T cell function, but with normal B and NK cells. Syk is the ZAP-70 analog in B cells.

TCR-APC Interaction. This video describes the process by which an antigen presenting cell interacts with a T cell. This video is from: Janeway's Immunobiology, 7th Edition Murphy, Travers, & Walport. Source: Garland Science.

Severe combined immunodeficiency (SCID) - 4 groups according to T/B/NK cells (click to enlarge the image).

Otelixizumab anti-CD3 antibody may be able to reverse autoimmune diseases, including Type 1 diabetes (Medscape, 2012).


T cell receptor (TCR) signaling

Published: 06/17/2009
Updated: 01/17/2012

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