Signals transduced by the TCR initiate a wide range of mature T cell responses. Signaling by the TCR and its precursor, the pre-TCR, are also involved in the thymocyte development and selection. And the TCR signal transduction is mediated by the ITAM (immunoreceptor tyrosine-based activation motifs). Among these, CD3-epsilon (CD3E)-mediated signals are supposed to be of significant importance in T cell development. Therapeutic approaches targeted CD3E is now involved in the development of the novel immune-modulating treatment for various diseases. Currently, Creative Biolabs is proud to offer the humanized CD3E knock-in mice, with customized technical support for your drug discovery studies.

CD3E Molecule and Signaling

CD3E, alternatively referred to as CD3-epsilon molecule, is a T cell surface single-pass type I membrane glycoprotein. It is a component of the T cell antigen receptor, which contains 1 Ig-like (immunoglobulin-like) domain and 1 ITAM (immunoreceptor tyrosine-based activation motifs) domain. CD3E, together with CD3-gamma, -delta and -zeta, and the T-cell receptor alpha/beta and gamma/delta heterodimers, forms the T cell receptor-CD3 complex. And this complex plays an essential role in coupling antigen recognition to several intracellular signal-transduction pathways. Thereinto, CD3E has a vital function in correct T-cell development.

Among all the CD3 subunits, CD3E is the expected candidate that performs an essential role in the T cell antigen receptor (TCR) signaling response, contributing to the survival of mature T cells. CD3E is represented twice in the TCR complex, serving as a component of both the gamma/epsilon and delta/epsilon dimers.

Research has shown that the cytoplasmic tail of the T cell receptor CD3E contains a phospholipid-binding motif, termed the basic-rich stretch (BRS), the positively charged residues of which enables this region of CD3 epsilon to complex a subset of acidic phospholipids, including PI(3)P, PI(4)P, PI(5)P, PI(3,4,5)P(3), and PI(4,5)P(2).

Magic™ Humanized CD3E Immune Checkpoint Knock-In MiceFig.1. Schematic representation of T-cell receptor signal transduction. (Zikherman & Weiss, 2009)

The Significance of CD3E Function

Above all, those studies represent a functional role of the CD3E binding domain in T cell biology. Another study has demonstrated that anti-CD3E antibody could inhibit T cell expansion in vivo and function as a protective role in graft-versus-host disease (GVHD), showing the implications for developing novel therapeutic approaches directed to TCR targeting in human diseases. Otherwise, the vital role of the TCR-CD3 complex in immunity is a major stimulus for discovering the molecular mechanisms by which it functions. Such knowledge will inform practical efforts with the intention of promoting T cell responses to tumor, vaccines, or pathogen. Definitely, the TCR-CD3 complex has always been targeted for the development of new immune-modulating agents.

Development of Humanized CD3E Knock-In Mice

Since CD3E serves as an essential role in the TCR signaling pathway, the development of agents targeting this reaction has generated great interest for novel drug development. Scientists in Creative Biolabs has established a set of well-characterized Magic™ “humanized” animal models via improved transgenic method. Our Magic™ humanized CD3E immune checkpoint KI mice with fully human CD3E gene are found to express the transgene protein and are ideal tools to evaluate novel immunotherapies. And the humanized CD3E KI mice are fully validated with treatment data and immunoprofiling, ensuring the effectiveness. Please feel free to contact us for more details.

Creative Biolabs also offers other various Humanized Mouse Models you may be interested in:

Reference

  1. Zikherman, J. and Weiss, A., Antigen receptor signaling in the rheumatic diseases. Arthritis research & therapy. 2009, 11(1):202.

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