Reviewer: S. Randhawa, M.D., Allergist/Immunologist
The cluster of differentiation (cluster of designation) (abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules present on leukocytes. There are approximately 300 different CD proteins.
|Type of cell||CD markers|
|all leukocyte groups||CD45+|
|T helper cell||CD45+,CD3+,CD4+|
|Cytotoxic T cell||CD45+,CD3+,CD8+|
|B lymphocyte||CD45+,CD19+ or CD45+,CD20+|
|Natural killer cell||CD16+,CD56+,CD3-|
List of human clusters of differentiation (CD)
CD1 - an MHC-like molecule that presents lipid molecules. There are 5 subsets - CD1a, b, c, d, e.
CD2 - a cell adhesion molecule on T cells and natural killer (NK) cells. Also called T-cell surface antigen T11/Leu-5, LFA-2, LFA-3 receptor, erythrocyte receptor, rosette receptor. CD2 is a ligand for CD58 and CD59 and is involved in signal transduction and cell adhesion; expressed in T-cell ALL and T-cell NHL. Alefacept (Amevive) is a LFA-3-IgG1 Fc fusion protein against CD2. It is used for treatment of moderate to severe plaque psoriasis.
CD3 - a component of the T cell receptor (TCR) complex, present on all T-lymphocytes. CD3 is not found on NK cells. CD3 defect causes T-B+ SCID.
CD4 - a co-receptor for MHC Class II; also a receptor used by HIV to enter T cells. Present on Th cells.
CD5 - a type I transmembrane protein found on T cells, thymocytes, and some B cells that is a ligand for CD72 and is involved in cellular activation or adhesion; expressed in B-cell CLL and T-cell NHL. A Ligand for CD5 Is CD5 (http://goo.gl/qsjT).
CD6 - adhesion molecule linking developing thymus-cells to thymus epithelial cells; co-stimulator to mature T cells.
CD7 - a type I transmembrane protein found on thymocytes, some T cells, monocytes, natural killer cells, and hemopoietic stem cells; expressed in patients with mycosis fungoides, some patients with T-cell ALL, and a few patients with acute nonlymphocytic lymphoma.
CD8 - a co-receptor for MHC Class I; also found on a subset of myeloid dendritic cells.
CD9 - a member of the Tetraspanin superfamily expressed in a variety of cells, including: pre B cells, eosinophils, basophils and platelets.
CD10 - a type II transmembrane protein found on pre-B cells, germinal-center B cells, some neutrophils, kidney cells, T-cell precursors, and epithelial cells that acts as a zinc metalloprotease cleaving peptide bonds on the amino side of hydrophobic amino acids; expressed in ALL and follicular-center-cell lymphomas.
CD11a - Subunit of LFA-1, a membrane glycoprotein that provides cell-cell adhesion by interaction with ICAM-1. Lymphocyte function-associated antigen 1 (LFA-1) consists of an alpha-chain (CD11a) and beta-chain (CD18). LAD type 1 (CD18 defect) is a problem of PMNs binding to integrins (LAF-1). Integration (tight adhesion) is the second phase of the PMN recruitment (see the "SIP" mnemonic below). LAD type 2 is a problem of PMNs binding to selectins. Selection ("rolling") is the first phase of the PMN recruitment (see the "SIP" mnemonic below). Efalizumab (Raptiva) is a humanized mAb against CD11a (α-subunit of leukocyte function antigen-1 [LFA-1]). It was used to treat moderate to severe plaque psoriasis. Due to the risk of PML, the European Medicines Agency and the FDA recommended suspension from the market in the European Union and the United States, respectively. In April, 2009, Genentech Inc. announced a phased voluntary withdrawal of Raptiva from the U.S. market.
CD11b - Subunit of MAC-1, a complement receptor (CR3). MAC-1 consists of an alpha-chain (CD11b) and beta-chain (CD18).
CD11c - Integrin alphaXbeta2 is a subunit of the complement receptor CR4. CR4 consists of an alpha-chain (CD11c) and beta-chain (CD18). CD11c is expressed in hairy cell leukemias, acute nonlymphocytic leukemias, and some B-cell CLL. CD11c is one of the defining markers for dendritic cells.
CD13 - a zinc metalloproteinase, also known as aminopeptidase N, which is found naturally on myelomonocytic cells from early differentiation through maturity; usually present on AML blasts and rarely found in some forms of lymphoma and lymphocytic leukemia.
CD14 - on macrophages, first described pattern recognition receptor (PRR, PAMP receptor), binds to bacterial LPS. Mnemonic: TLR4 and CD14 recongnize LPS. Monocytes are CD45+ CD14+.
CD15 - a carbohydrate adhesion molecule (not a protein) that mediates phagocytosis and chemotaxis. CD15 is also called Sialyl LewisX (SLeX) and SSEA-1 (stage specific embryonic antigen 1). LAD type 1 is a problem of PMNs binding to integrins (LAF-1). Integration (tight adhesion) is the second phase of the PMN recruitment (see the "SIP" mnemonic below). LAD type 2 (CD15 defect) is a problem of PMNs binding to selectins. Selection ("rolling") is the first phase of the PMN recruitment (see the "SIP" mnemonic below). Granulocytes are CD45+ CD15+.
CD16 - FcγRIII, a low-affinity Fc receptor for IgG. Found on NK cells, macrophages, and neutrophils. CD16 is the most common IgG Fc receptor. NK cells are CD45+ CD3- CD16+ or CD56+. NKT cells are CD45+ CD3+ CD16+ or CD56+.
CD18 - CD18 is the beta subunit of 3 different structures (paired with CD11 a, b, c): LFA-1 (paired with CD11a), Macrophage-1 antigen, MAC-1 (paired with CD11b), Integrin alphaXbeta2 (paired with CD11c). CD18 helps neutrophils make their way from the blood stream into the infected areas of the body. LAD type 1 (CD18 defect) is a problem of PMNs binding to integrins (LAF-1). Integration (tight adhesion) is the second phase of the PMN recruitment (see the "SIP" mnemonic below). LAD type 2 is a problem of PMNs binding to selectins. Selection ("rolling") is the first phase of the PMN recruitment (see the "SIP" mnemonic below).
CD19 - B-lymphocyte surface antigen. Probably the best marker of B-lymphocytes. CD19 is a co-receptor with CD21. Complement receptor CD21 (CR2) activates BCR if the antigen is opsonized by C3b component of the complement. CR2-CD19-CD81 complex is expressed on the surface of B lymphocytes. When CD21 (CR2) interacts with C3d, the complex is brought into the BCR. CD19 has an ITAM that is phosphorylated, thus recruiting Lyn to enhance phosphorylation.
CD20 - found on B cells, forms a calcium channel for influx of calcium required for cell activation; expressed in B-cell lymphomas, hairy cell leukemia, and B-cell CLL. Rituximab is an antibody against CD20, used for treatment of CLL. Anti-CD20 monoclonal antibody ocrelizumab helps patients with relapsing-remitting multiple sclerosis (MS) (Lancet, 2011).
CD21 (CR2) - found on B cells and follicular dendritic cells, plays a role in signal transduction. CD19 is a co-receptor with CD21. Complement receptor CD21 (CR2) activates BCR if the antigen is opsonized by C3b component of the complement. CR2-CD19-CD81 complex is expressed on the surface of B lymphocytes. CD21 is receptor for complement (CD21(CR2) binds C3d) and Epstein-Barr virus (EBV). CD21 (CR2) binds EBV, HHV8, C3d, and CD23 (low affinity IgE receptor (FceRII). CD21(CR2) is expressed in hairy cell leukemia, B-cell lymphoma, and some T-cell ALL.
CD22 is a B-lymphocyte cell adhesion molecule (BL-CAM)that binds sialic acid with an immunoglobulin (Ig) domain. CD22 is a member of Ig superfamily and SIGLEC family. CD22 is an inhibitory receptor for B cell receptor (BCR) signalling.
CD23 is the low affinity IgE receptor (FceRII). CD21 (CR2) binds EBV, HHV8, C3d, and CD23 (low affinity IgE receptor (FceRII).
CD24 - a glycoprotein expressed on the surface of most B lymphocytes and differentiating neuroblasts.
CD25 - a transmembrane protein present on activated T and B cells, myeloid precursors, and oligodendrocytes. CD25 associates with CD122 to form a heterodimer that acts as a high-affinity receptor for IL-2. CD15 is IL-2R-alpha chain. CD25 is expressed in most B-cell neoplasms, some acute nonlymphocytic leukemias, and neuroblastomas. Daclizumab is an antibody against CD25. CD 25 is one the defining markerks of T-reg cells (CD4+/CD25+/Foxp3+).
CD26 - membrane-bound protease. T-cell costimulatory molecule. Cell adhesion molecule.
CD27 - TNF-receptor and a marker of memory B cells. CD27 is the defining marker of B memory cells, just like CD25 is one of the defining markers of T-reg cells (CD4+/CD25+/Foxp3+). CD27 is a member of the TNFRSF (TNF receptor superfamily). TNFRSF includes CD27, CD30, CD40, FAS, CD120, CD134, CD137. Memory B cells are CD19+ CD27+ sIgM+. Switched memory B cells are CD19+ CD27+ sIgM-.
CD28 - present on all T-cells, and when matched with the appropriate ligand (CD80 or CD86), it has co-stimulatory effect on T-cells. CD28 is also expressed on eosinophil granulocytes, especially after tissue infiltration.
CD29 - integrin beta-1 - a cell adhesion molecule.
CD30 - present on activated T and B cells. CD30 is expressed in Hodgkin disease, some T-cell lymphomas, and anaplastic large cell lymphomas. CD30 is a member of the TNFRSF. TNFRSF includes CD27, CD30, CD40, FAS, CD120, CD134, CD137.
CD31 - PECAM-1, a cell adhesion molecule on platelets and endothelial cells. CD31 is from Ig superfamily, it binds CD38.
CD32 - FcγRII, a receptor for the Fc (constant) region of immunoglobulin G (IgG). CD32 down-regulates IgG. Binding of FcγRIIb is the proposed mechanism of action of IVIG.
CD33 - found on immature myeloid cells, including acute myeloid leukemia blasts and mature monocytes.
CD34 - stem cell marker and adhesion molecule. CD34 is found on hematopoietic precursors (high concentrations in umbilical cord blood) and embryonic fibroblasts. CD34 is the defining marker of stem cells. CD34 binds CD62L (L selectin).
CD35 - complement receptor 1 (C3b/C4b receptor). Complement receptor (CR2) is CD21 - it activates BCR if the antigen is opsonized by C3b component of the complement. CR2-CD19-CD81 complex is expressed on the surface of B lymphocytes.
CD36 - Platelet glycoprotein IV or IIIb (GP IV / GP IIIb).
CD37 - A leucocyte restricted tetraspanin expressed primarily in B cells, but also found on T cells, monocytes and granulocytes.
CD38 - involved in ecto-ADP-ribosyl cyclase and cell activation on many hematopoietic, plasma, and B and T activated cells; marker increases with HIV seroconversion, coexpression with CD8 associated with progression (indicates persistent viral stimulation).
CD40 - a co-stimulatory protein found on antigen presenting cells. CD40 combines with CD154 (CD40L) on T cells to induce antibody isotype switching in B cells. CD40 and CD40L (CD154) defect leads to hyperIgM syndrome (HIGM3). TNFRSF includes CD27, CD30, CD40, FAS, CD120, CD134, CD137.
CD41 - platelet glycoprotein (GPIIb/IIIa) integrin acts as a receptor for fibrinogen and several other extracellular matrix molecules. Its absence causes Glanzmann's thrombasthenia.
CD42 - platelet glycoprotein Ib/V/IX complex(GPIb/V/IX). Expressed on platelets and is a late, specific marker of megakaryocyte differentiation. The glycoprotein Ib/V/IX complex is essential for normal haemostasis; deficiency results in Bernard-Soulier Syndrome, a syndrome of thrombocytopenia and giant platelets.
CD43 - a sialomucin.
CD44 - a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. PMN adhesion to the endothelium is mediated through CD44.
CD45 - leukocyte common antigen (LCA), protein tyrosine phosphatase, receptor type, C (PTPRC). CD45 is a type I transmembrane protein present on all hematopoietic cells, except erythrocytes. Various isoforms of CD45 exist, memory T lymphocytes express the shortest CD45 isoform, CD45RO. CD45RA is present on naïve T cells. CD45RO is present on memory T cells. CD45 is defective in T-B+NK+ SCID.
CD46 - inhibitory complement receptor which is ubiquitously expressed on human cells. CD46 is a membrane cofactor protein (MCP).
CD47 - Membrane protein, which is involved in the increase in intracellular calcium concentration that occurs upon cell adhesion to extracellular matrix.
CD49a-f - Very late antigen (VLA). CD49 (VLA) is present on WBCs. VLA participates in cell adhesion.
CD53 - A leucocyte restricted tetraspanin expressed by B cells, T cells, dendritic cells, monocytes, NK cells and granulocytes.
CD54 - Intercellular adhesion molecule -1 (ICAM-1). CD54 (ICAM-1) binds LFA-1 (CD50) and is a receptor for rhinovirus.
CD55 - complement Decay-Accelerating Factor (DAF). CD55 (DAF) prevents the assembly of the C3bBb complex (the C3-convertase of the alternative pathway) or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex (MAC). CD55 is deficient in paroxysmal nocturnal hemoglobinuria (PNH). CD59 absence also leads to PNH.
CD56 - NCAM (neural cell adhesion molecule), a marker for natural killer (NK) cells and some T-lymphocytes. NK cells are CD45+ CD3- CD16+ or CD56+. NKT cells are CD45+ CD3+ CD16+ or CD56+.
CD58 (LFA-3) - a membrane protein present on many hemopoietic cells and fibroblasts that acts as a ligand for CD2 and may be involved in T-cell function.
CD59 - Protectin or Membrane attack complex inhibition factor (MACIF); MAC-inhibitory protein (MAC-IP). CD59 inhibits MAC which consists of C5-9 (mnemonic). CD59 or CD55 absence leads to paroxysmal nocturnal hemoglobinuria (PNH).
CD61 - Integrin beta 3 (Itgb3); Glycoprotein IIIa (GPIIIa): fibrinogen receptor; major role is in platelet aggregation. Defects in Itgb3 cause Glanzmann's thrombasthenia. Platelets are CD45+ CD61+.
CD62E - E-selectin is a cell adhesion molecule expressed on Endothelial cells activated by cytokines. CD62E is a ligand for CD15, CD44, and CD162. CD62E and CD15 are defective in LAD2.
CD62L - L-selectin is a cell adhesion molecule found on Leukocytes. CD62L binds CD34, CD15 and MADCAM. Central memory T cells are CD27+, CCR7+, CD62L+.
CD62P - P-selectin is a cell adhesion molecule (CAM) found in granules in endothelial cells and activated Platelets. CD62P binds CD162.
CD64 is a is a high affinity IgG receptor, FcγRI.
CD66 - CEA, a cell adhesion molecule (CAM) of Ig superfamily.
CD68 - highly glycosylated transmembrane protein which is mainly located in lysosomes. Present in macrophages in many human tissues including Kupffer’s cells and macrophages in the red pulp of the spleen, in lung alveoli, in lamina propria of the gut, and in the bone marrow. Used as immunocytochemical marker for staining of monocytes/macrophages.
CD69 - An early activation marker on T cells and NK cells.
CD71 - Transferrin receptor, mediates cellular uptake of iron.
CD72 - Mediator of B- and T-cell interactions.
CD80 - when bound to CD28 on T-cells, can provide the costimulatory effect; also referred to as B7.1, one of the B7 molecules. Causes up-regulation of a high affinity IL-2 receptor allowing T cells to proliferate. Abatacept (Orencia) is CTLA4-human IgG1 fusion protein against B7-1 (CD80) and B7-2 (CD86). It us used for treatment of rheumatoid arthritis and juvenile rheumatoid arthritis.
CD81 - A tetraspanin expressed in a wide variety of tissues, which plays an important role in B cells as part of the B cell co-receptor complex with CD19, Leu 13 and CD21. Also expressed in T cells, NK cells, Dendritic cells, Monocytes and blood progenitors.
CD82 - Member of the tetraspanin family of transmembrane proteins. Broad tissue distribution including B cells, T cells, Granulocytes, Monocytes and CD34+ progenitors.
CD83 - a transmembrane glycoprotein of the Ig superfamily. Expressed on cultured dendritic cells, interdigitating, follicular, and circulating dendritic cells as well as some proliferating lymphocyte of all human cell lines.
CD86 - when bound to CD28 on T-cells, can provide the costimulatory effect; also referred to as B7.2, one of the B7 molecules. Causes up-regulation of a high affinity IL-2 receptor allowing T cells to proliferate. Abatacept (Orencia) is CTLA4-human IgG1 fusion protein against B7-1 (CD80) and B7-2 (CD86). It us used for treatment of rheumatoid arthritis and juvenile rheumatoid arthritis.
CD87 - also referred to as the urokinase type plasminogen activator receptor, provides a binding point for urokinase type plasminogen activator.
CD88 - C5a receptor.
CD89 - FcalphaRI - receptor for IgA.
CD90 Thy-1 - Thymus cell antigen.
CD91 - Low density lipoprotein (LDL) receptor-related protein 1 (LRP1) (also known as α2-macroglobulin receptor), a major endocytotic receptor with over 35 known ligands including amyloid precursor protein (APP), ApoE, and many proteins involved with protease regulation.
CD95 - Fas Receptor, a receptor for Fas ligand, an extrinsic apoptotic signal. Its aliases include CD95/FasR, Apo-1, and tumor necrosis factor receptor superfamily, member 6 (TNFRSF6). CD95 (Fas) causes apoptosis when ligated by FasL. CD178 is Fas ligand. CD178 (FasL) binds CD95 (Fas) and causes apoptosis. CD95 (Fas) is defective in ALPS.
CD99 - CD44 and CD99 - both participate in leukocyte migration. CD99 is expressed on all leukocytes but highest on thymocytes and augments T-cell adhesion, apoptosis of double positive T cells, and participates in migration and activation.
CD103 - a type I transmembrane protein present on intestinal intraepithelial lymphocytes, some circulating leukocytes, and some T cells that facilitates adhesion to epithelia; expressed in hairy cell leukemia and some B-cell CLL.
CD105 - Endoglin, a regulatory component of the TGF-beta receptor-cell complex. Mediates cellular response to TGFbeta.
CD106 - VCAM-1 is an adhesion molecule involved in white blood cell migration.
CD117 (C-kit) is required for mast cell survival and is the ligand for stem cell factor (SCF).
CD120 - a member of the TNFRSF (like CD27, CD30, CD40, FAS).
CD127 - IL-7 receptor alpha chain. Thymic stromal lymphopoietin (TSLP) signals through a heterodimeric receptor complex composed of the TSLP receptor and the IL-7R alpha chain. Some researchers have classified TSLP as a "master regulator" of the Th2 response due to overexpression of the cytokine in pulmonary tissue and skin cells result in Th2-induced asthma and dermatitis. A defect in IL-7RA leads to SCID (T-/B+/NK+). Anti-TSLP is a potential new therapeutic target in asthma.
CD142 - Tissue factor, a major initiator of blood-clotting.
CD143 - Angiotensin-converting enzyme.
CD144 - Cadherin, a calcium-dependent adhesion molecule at intercellular junctions, found mainly in the vascular endothelium. Recent research indicates that CD144 may be present on some leucocytes as well.
CD152 - Cytotoxic T-lymphocyte antigen-4 (CTLA-4). CTLA-4 binds to CD80 and CD86 receptors with a higher affinity than CD28, and inhibits T cell activation.
CD154 (CD40L) - ligand for CD40. CD154 is a co-stimulatory molecule that plays many roles, best known for activating B cells but it also activates APCs in association with T cell receptor stimulation by MHC molecules.
CD158 - KIR expressed on NK and T cells. CD158 binds HLA class I and inhibits NK or T cell cytotoxicity.
CD159 is expressed on NK cells and modulates NK killing.
CD162 is a P-selectin glycoprotein ligand-1 (PSGL-1). CD162 binds to CD62P.
CD163 - M130; HbSR; RM3/1 antigen. A glycoprotein endocytic scavenger receptor for haptoglobin-hemoglobin complexes. Found specifically on monocytes/macrophages and some dendritic cells. Involved in anti-iflammatory processes. Soluble form shed upon Toll-like receptor activation.
CD166 - activated leukocyte cell adhesion molecule (ALCAM).
CD178 is Fas ligand. CD178 (FasL) binds CD95 (Fas) and causes apoptosis.
CD209 - DC-SIGN, C-type lectin receptor found on dendritic cell subsets.
CD303 - BDCA-2, a type II transmembrane C-type lectin which is involved in endocytosis of antigens for processing in plasmacytoid dendritic cells. Activation decreases type I interferon production.
References and related reading
Cluster of differentiation, Wikipedia.
List of human clusters of differentiation (CD), Wikipedia.
TSLP calms inflammation. The Journal of Experimental Medicine, Vol. 206, No. 3, 493, 2009.
Immunomodulatory Receptor CD300a http://goo.gl/36OCR - In other news, there are now officially more than 300 CD markers!