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 63 (CD63) is a member of the CD family and the transmembrane 4 superfamily,also known as the tetraspanin family. CD63 is a cellular surface glycoprotein characterized by the presence of four bydrophobic domains. CD63 had functions in mediating signal transduction processes and then regulate variety of cellular processes such as cell proliferation, activation and motility. It has reported that CD63 protein associated with tumor progression and served as a blood platlet activation marker and the deficiency of this protein may be associated with Hermansky-Pudlak syndrome.
Macrosialin, also known as CD68 and Gp110, is a single-pass type I membrane protein which belongs to theLAMP family. CD68 is highly expressed by blood monocytes and tissue macrophages. It is also expressed in lymphocytes, fibroblasts and endothelial cells. CD68 is expressed in many tumor cell lines which could allow them to attach to selectins on vascular endothelium, facilitating their dissemination to secondary sites. CD68 plays a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. It is a commonly used marker for macrophages. However, a number of studies have shown that CD68 antibodies react with other hematopoietic and non-hematopoietic cell types, suggesting that CD68 may not be a macrophage-specific antigen. CD68 binds to tissue- and organ-specific lectins or selectins, allowing homing of macrophage subsets to particular sites. Rapid recirculation of CD68 from endosomes and lysosomes to the plasma membrane may allow macrophages to crawl over selectin-bearing substrates or other cells.
CD68, also called Scavenger Receptor D1 (SR-D1) and LAMP-4, is a heavily glycosylated type I transmembrane glycoprotein that belongs to the LAMP family. CD68 is expressed in many tumor cell lines which could allow them to attach to selectins on vascular endothelium, facilitating their dissemination to secondary sites. CD68 plays a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. It is a commonly used marker for macrophages. CD68 is also a biomarker of rheumatoid arthritis and Hodgkin's lymphoma. CD68 influences the functions of cells through NF-kB/focal adhesion kinase pathway (7). In addition, CD68 on macrophages binds tightly to both S100A8 and S100A9 to enhance the cell immunity.
Early activation antigen CD69, also known as activation inducer molecule (AIM), is a single-pass type II membrane protein. Recently, cDNA clones encoding human and mouse CD69 were isolated and showed CD69 to be a member of the C-type lectin superfamily. It is one of the earliest cell surface antigens expressed by T cells following activation. Once expressed, CD69 acts as a costimulatory molecule for T cell activation and proliferation. In addition to mature T cells, CD69 is inducibly expressed by immature thymocytes, B cells, natural killer (NK) cells, monocytes, neutrophils and eosinophils, and is constitutively expressed by mature thymocytes and platelets. CD69 is involved in lymphocyte proliferation and functions as a signal transmitting receptor in lymphocytes, natural killer (NK) cells, and platelets. The structure, chromosomal localization, expression and function of CD69 suggest that it is likely a pleiotropic immune regulator , potentially important in the activation and differentiation of a wide variety of hematopoietic cells. This membrane molecule transiently expresses on activated lymphocytes, and its selective expression in inflammatory infiltrates suggests that it plays a role in the pathogenesis of inflammatory diseases. CD69 plays a crucial role in the pathogenesis of allergen-induced eosinophilic airway inflammation and hyperresponsiveness and that CD69 could be a possible therapeutic target for asthmatic patients.
Human Early Activation Antigen CD69 (CD69) is a type 2 transmembrane glycoprotein in the C-type lectin family. It plays roles in immune cell trafficking, inflammation, T cell memory, and humoral immune responses. CD69 is expressed on the cell surface as an approximately 60 kDa disulfide-linked homodimer. It is found on CD4+ T cells, CD8+ T cells, NK cells, NKT cells, gamma delta cells dendritic cells (DC) and is up-regulated on activated T cells and DC. Ligation of CD69 on DC induces IL2 production, leading to T cell proliferation. CD69 is important for the homing of CD4+ T cells and plasmablasts to the bone marrow but inhibits the migration of dermal DC to draining lymph nodes. It supports the expression of multiple chemokines and chemokine receptors but suppresses the expression of others. It associates with and negatively regulates S1P1 expression on DC and CD4+ T cells, resulting in a decreased chemotactic response to S1P. The direct interaction of CD69 with Galectin-1 contributes to the ability of CD69 to limit Th17 mediated inflamamtion while supporting the differentiation of regulatory T cells.
This gene encodes a protein found on the outer membrane of T-lymphocytes as well as some other immune cells. The encoded protein contains three scavenger receptor cysteine-rich (SRCR) domains and a binding site for an activated leukocyte cell adhesion molecule. The gene product is important for continuation of T cell activation. This gene may be associated with an susceptibility to multiple sclerosis (PMID: 19525953, 21849685). Multiple transcript variants encoding different isoforms have been found for this gene.
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