T-cell surface glycoprotein CD3 epsilon chain, also known as CD3E, is a single-pass type I membrane protein. CD3E contains 1 Ig-like (immunoglobulin-like) domain and 1 ITAM domain. CD3E, together with CD3-gamma, CD3-delta and CD3-zeta, and the T-cell receptor alpha/beta and gamma/delta heterodimers, forms the T cell receptor-CD3 complex. The CD3 epsilon subunit of the T cell receptor (TCR) complex contains two defined signaling domains, a proline-rich sequence and an immune tyrosine activation motifs (ITAMs), and this complex undergoes a conformational change upon ligand binding that is thought to be important for the activation of T cells. T cell receptor-CD3 complex plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. This complex is critical for T-cell development and function, and represents one of the most complex transmembrane receptors. CD3E plays an essential role in T-cell development, and defects in CD3E gene cause severe immunodeficiency. Homozygous mutations in CD3D and CD3E genes lead to a complete block in T-cell development and thus to an early-onset severe combined immunodeficiency phenotype.
CD40 is a Type I Transmembrane Glycoprotein that belongs to the TNF Receptor Superfamily. CD40 is expressed in B cells, follicular dendritic cells, dendritic cells, activated monocytes, macrophages, endothelial cells, vascular smooth muscle cells, and several tumor cell lines. The extracellular domain of CD40 is characterized by Cysteine rich repeat regions. Interaction of CD40 with its ligand (CD40L) leads to aggregation of CD40 molecules, which in turn interact with cytoplasmic components to initiate signaling pathways. Several different TRAF proteins (adaptor proteins) have been identified to serves as mediators of the signal transduction.
T-Cell Antigen CD7 is a single-pass type I membrane protein that that belongs to the the immunoglobulin superfamily. Human CD7 is synthesized as a 240 amino acid precursor that contains a 25 amino acid signal sequence and a 215 amino acid mature chain with a Ig-like (immunoglobulin-like) domain. CD7 is normally expressed on all T-lymphocytes, NK-cells, pre-B lymphocytes and pleuripotent hematopoietic stem cells. CD7 plays an essential role in T-cell interactions, T-cell/B-cell interaction during early lymphoid development, T- and NK-cell activation and cytokine production. CD7 has been shown to interact with PIK3R1and SECTM1. However, the function of the CD7 protein in the immune system is still largely unknown.
Cytotoxic and Regulatory T-Cell Molecule (CRTAM) is a member of Nectin family under the immunoglobulin superfamily that is expressed by activated CD8+ and NK T cells. CRTAM is found in spleen, thymus, small intestine, peripheral blood, and it is highly expressed by Purkinje cells of the cerebellum. CRTAM is a type I transmembrane glycoprotein containing one Ig-like C2-type domain and one Ig-like V-type domain in its extracellular domain, while its cytoplasmic region shows a potential class I PDZ domain. CRTAM is expressed as a homodimer on the cell surface but does not show homotypic binding in trans. The high affinity of CRTAM/IGSF4 adhesion allows CRTAM to disrupt IGSF4 homotypic interactions. IGSF4 and T cell receptor coengagement of CD8+ cells expressiong CRTAM induces increased IFNγ or IL-22 production.
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