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.
C-Type Lectin Domain Family 3 Member B (CLEC3B) is a serum and tissue protein and it contais a C-type lectin which binds to Ca++. CLEC3B is originally found in plasma, the concentrations approximately 10mg/l. It can bind to kringle 4 of plasminogen and enhance the activation of plaminogen to plasmin, catalyzed by tissue plasminogen activator in the presence of poly-D-lysine. In addition, CLEC3B may be involved in the packaging of molecules destined for exocytosis. Also, CLEC3B is best known as a prognostic marker in ovarian cancer.
Dendritic cell immunoreceptor (DCIR), also known as CLEC4A, CLECSF6, is a single-pass type II C-type lectin receptor expressed mainly in dendritic cells (DCs), which is a negative regulator of DC expansion and has a crucial role in maintaining the homeostasis of the immune system. These type II receptors contain a single extracellular carbohydrate recognition domain and have diverse functions in both immunity and homeostasis. DCIR is the only member of the family which contains a cytoplasmic signalling motif and has been shown to act as an inhibitory receptor, while BDCA-2, Dectin-2, DCAR and Mincle all associate with FcRgamma chain to induce cellular activation, including phagocytosis and cytokine production. Dectin-2 and Mincle have been shown to act as pattern recognition receptors for fungi, while DCIR acts as an attachment factor for HIV. In addition to pathogen recognition, DCIR has been shown to be pivotal in preventing autoimmune disease by controlling dendritic cell proliferation. DCIR expressed on antigen presenting cells and granulocytes and acts as an inhibitory receptor via an intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM). It may also be involved via its ITIM motif in the inhibition of B-cell-receptor-mediated calcium mobilization and protein tyrosine phosphorylation. Additionally, DCIR can participate in the capture of HIV-1 and promote infection in trans and in cis of autologous CD4(+) T cells from human immature monocyte-derived DCs. DCIR acts as a ligand for HIV-1 and is involved in events leading to productive virus infection.
C-type lectin (CLEC) family is a type of carbohydrate-binding protein domain named lectin. C-type lectins are the most diverse and prevalent lectin family in immunity with its requirement for calcium for binding. Proteins including a C-type lectin domain have diverse range of functions including cell-cell adhesion, immune response to pathogens and apoptosis. There are at least 14 types of C-type lectins: typeⅠto typeⅩⅣ. CLEC4D(CLECSF8) is a typeⅡ membrane glycoprotein belonging to the C-type lectin family, with restricted expression in the monocyte/macrophage lineage. It plays important roles in the function of macrophages.
C-Type Lectin Domain Family 4 Member E (CLEC4E) is a 219 amino acid single-pass type II membrane protein that contains one C-type Lectin domain. It is expressed in monocytes, CLEC4E functions as a downstream target of C/EBP β and is thought to play a role in the inflammatory response, possibly via transcriptional control of C/EBP β. CLEC4E may play a role in the response to inflammatory stimuli in peritoneal macrophages and may be involved in immune surveillance processes under transcriptional control of CEBPB. Human CLEC4E shares 67% sequence identity with its mouse counterpart, suggesting a similar function between species. CLEC-4E exists as multiple alternatively spliced isoforms that are encoded by a gene which maps to a natural killer gene complex region on human chromosome 12.
Chloride Intracellular Channel Protein 1 (CLIC1) belongs to the Chloride Channel CLIC family and contains one GST C-terminal domain. CLIC1 can be expressed in various cell types, but it is especially prominent in the heart, placenta, liver, kidney, and pancreas. CLIC1 can insert into membranes and form chloride ion channels. The channel activity depends on the pH. CLIC1 membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions. CLIC1 is also involved in the regulation of the cell cycle.
Chloride Intracellular Channel Protein 2 (CLIC2) is a critical component of all living cells; it regulatescellular traffic of Chloride ion and it can be inserted into membranes anf form chloride ion channels. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions, channel activity depends on the pH. CLIC2 is involved in regulating membrane potential and organic solute transport. CLIC2 modulates the activity of RYR2 and inhibits Calcium influx. CLIC2 can be detected in the adult brain, liver, lung, heart, stomach, spleen and testis. It is expressed in fetal liver and adult skeletal muscle. CLIC2 is a potential candidate for one of many diseases linked to Xq28.
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