CD247, also known as CD3-ZETA, belongs to the CD3Z/FCER1G family. It contains 3 ITAM domains. As a-cell receptor zeta, CD247 forms the T-cell receptor-CD3 complex together with T-cell receptor alpha/beta and gamma/delta heterodimers, and with CD3-gamma,-delta and &ndash,epsilon. The zeta chain plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. Low expression of the antigen results in impaired immune response. Two alternatively spliced transcript variants encoding distinct isoforms have been found for CD247 gene. Defects in CD247 can cause immunodeficiency due to defect in CD3-zeta. An immunological deficiency characterized by T-cells impaired immune response to alloantigens, tetanus toxoid and mitogens. CD247 may play a role in assembly and expression of the TCR complex as well as signal transduction upon antigen triggering.
The cluster of differentiation (CD) system is commonly used as cell markers in immunophynotyping. Different kinds of cells in the immune system can be identified through the surface CD molecules which associating with the immune function of the cell. There are more than 320 CD unique clusters and subclusters have been identified. Some of the CD molecules serve as receptors or ligands important to the cell through initiating a signal cascade which then alter the behavior of the cell. Some CD proteins do not take part in cell signal process but have other functions such as cell adhesion. Cluster of differentiation 24, also known as signal transducer CD24 or heat stable antigen CD24 (HSA), is a mucin-type glycosylphosphatidylinositol-linked glycoprotein expressed on the surface of B-cells, differentiating neuroblasts and many tumors. It is involved in molecular adhesion and metastatic tumor spread and serve as a normal receptor for P-selectin. The CD24 / P-selectin pathway could be important in dissimenating of tumor cells by facilitating the interaction with platelet and endothelial cells. It has also been considered as a tumor marker. High rate of CD24 expressions have been found in epithelial ovarian cancer, breast cancer, non-small cell lung cancer, prostate cancer and pancreatic cancer.
Signal Transducer CD24 is a heavily and variably glycosylated GPI-linked sialoprotein. Human CD24 is expressed on B lineage cells and granulocytes, on epithelial, neuronal, and muscle cells, and on a range of tumor cells. CD24 expression is regulated during lineage development and with the activation of various cell types. Antibody crosslinking of CD24 enhances the induction of apoptosis in B and T lymphocytes which contributes to negative selection and the induction of immune tolerance. CD24 on antigen presenting cells cooperates with B7 molecules in the costimulation of T cells. CD24 associates in cis with Siglec10 and with the danger-associated molecules HMGB1, HSP70, or HSP90 which are released from necrotic or damaged cells. Formation of these ternary complexes fills a protective role: the resulting Siglec10 signaling inhibits inflammatory responses that are otherwise induced by extracellular DAMPs.
Programmed cell death ligand 1(CD274,or B7-H1,PD-L1),is the first member of B7 family to be discovered. B7 family molecules are type I transmembrane proteins belonging to the immunoglobulin superfamily. In concert with an their CD28 family receptors,the B7s are key regulators of the adaptive immune response. CD274 is suggested a negative regulator of T and B cell,and play important role in mediating tolerance of lymphocytes to self-antigens. It also involved in the costimulatory signal,essential for T-cell proliferation and production of IL10 and IFNG,in an IL2-dependent and a PDCD1-independent manner. PD-L1 is a 290 aa transmembrane protein with an a calculated molecular weight of 33 kDa,the apparent molecular weight has been reported as 45-70 kDa,suggesting probable glycosylation .
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