CD Antigens

Key Biological Properties: CD3 is a highly related cell-surface protein of the immunoglobulin superfamily containing a single extracellular immunoglobulin domain . The transmembrane region of the CD3 chains is negatively charged, allowing these chains to associate with the positively charged TCR chains .

Expression Patterns and Tissue Distribution: CD3 is expressed on the surface of T cells, which are a type of white blood cell central to the immune response . The CD3 complex is tightly associated with the T cell receptor, which recognizes specific antigens presented by other cells .

Primary Biological Functions: The primary function of CD3 is to transmit signals from the T cell receptor (TCR) to the inside of the T cell . When the TCR recognizes and binds to an antigen, CD3 helps initiate a cascade of intracellular events that activate the T cell .

Role in Immune Responses and Pathogen Recognition: CD3 is crucial for the activation of T cells, which are essential for attacking infected or cancerous cells and coordinating the immune response . It plays a vital role in the TCR signaling pathway, influencing the positive and negative selection of thymic T cells, regulating cell surface receptor signaling pathways, and promoting T cell differentiation and activation .

Mechanisms with Other Molecules and Cells: The CD3 complex serves as a T cell co-receptor that associates noncovalently with the T cell receptor (TCR) . The TCR cannot bind free epitopes/antigen; instead, it binds enzymatically cleaved fragments of larger polypeptides associated with major histocompatibility complexes (MHC) .

Binding Partners and Downstream Signaling Cascades: Upon antigen stimulation, the intracellular domains of CD3 undergo conformational changes. Src family protein tyrosine kinases (PTKs) then phosphorylate the tyrosine residues within the immune receptor tyrosine activation motif (ITAM) of the TCR/CD3 complex . This phosphorylation creates docking sites for proteins containing SH2 domains, such as ZAP-70, which subsequently initiates downstream signaling pathways .

Regulatory Mechanisms Controlling Expression and Activity: The expression and activity of CD3 are regulated through various mechanisms, including transcriptional regulation and post-translational modifications . Phosphorylation of the ITAM on CD3 renders the CD3 chain capable of binding an enzyme called ZAP70, a kinase that is important in the signaling cascade of the T cell .

Transcriptional Regulation and Post-Translational Modifications: Dynamic regulation of TCR/CD3 complexes on the cell surface plays a critical role in controlling antigen-dependent T cell-mediated immune responses .

Biomedical Research: CD3 is extensively used in biomedical research to study T cell activation and immune responses .

Diagnostic Tools: Anti-CD3 antibodies are used in several scientific applications, including Flow Cytometry, Immunohistochemistry, Western Blot, Immunocytochemistry, and Immunoprecipitation .

Therapeutic Strategies: Monoclonal antibodies against CD3 are used to modulate the immune response in diseases like type 1 diabetes and in preventing organ transplant rejection . CD3ε is critical for bispecific antibodies and immunotherapy, CD3δ shows promise in treating immune deficiencies, and CD3ζ plays a crucial role in CAR-T therapy .

Role Throughout the Life Cycle: CD3 plays a significant role throughout the life cycle, from development to aging and disease. It is involved in the positive and negative selection of thymic T cells, which is crucial for the development of a functional and self-tolerant T cell repertoire . CD3 also regulates various signaling pathways, including the transmembrane receptor protein tyrosine kinase signaling pathway and the apoptosis signaling pathway, significantly impacting gene expression and apoptosis processes .