Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways (PubMed:2470098). In addition of this role of signal transduction in T-cell activation, CD3E plays an essential role in correct T-cell development. Initiates the TCR-CD3 complex assembly by forming the two heterodimers CD3D/CD3E and CD3G/CD3E. Participates also in internalization and cell surface down-regulation of TCR-CD3 complexes via endocytosis sequences present in CD3E cytosolic region
CD3ε is a 20 kD transmembrane protein, also known as CD3 or T3. It is a member of the Ig superfamily and primarily expressed on T cells, NK-T cells, and at different levels on thymocytes during T cell differentiation. CD3ε forms a TCR complex by associating with the CD3δ, γ and ζ chains, as well as the TCR α/β or γ/δ chains. CD3 plays a critical role in TCR signal transduction, T cell activation, and antigen recognition by binding the peptide/MHC antigen complex.
CD40 is a 48 kD type I transmembrane glycoprotein also known as Bp50. It is a member of the tumor necrosis factor receptor (TNFR) superfamily and is expressed on B cells, basal epithelial cells, macrophages, follicular dendritic cells, endothelial cells, and a subset of CD34+ hematopoietic progenitors. CD40 regulates B cell development/maturation, Ig isotype switching and, in combination with other signals such as IL-4, protects B cells from surface Ig-induced apoptosis and promotes proliferation. Interaction of CD40 with its ligand CD154 (gp39), which is expressed on activated T cells, is important in costimulation and immune regulation.
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