Cluster of differentiation (CD) of leukocytes

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology

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 250 different CD proteins.

Type of cell	CD markers
stem cells	CD34+,CD31-
all leukocyte groups	CD45+
Granulocyte	CD45+,CD15+
Monocyte	CD45+,CD14+
T lymphocyte	CD45+,CD3+
T helper cell	CD45+,CD3+,CD4+
Cytotoxic T cell	CD45+,CD3+,CD8+
B lymphocyte	CD45+,CD19+ or CD45+,CD20+
Thrombocyte	CD45+,CD61+
Natural killer cell	CD16+,CD56+,CD3-

List of human clusters of differentiation (CD)

CD1 - an MHC-like molecule that presents lipid molecules.

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.

CD3 - a component of the T cell receptor (TCR) complex, present on all T-lymphocytes.

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.

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).

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 (PAMP receptor), binds to bacterial LPS.

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).

CD16 - FcγRIII, a low-affinity Fc receptor for IgG. Found on NK cells, macrophages, and neutrophils.

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.

CD20 - a type III transmembrane protein found on B cells that forms a calcium channel in the cell membrane allowing for the 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.

CD21 - a type I transmembrane protein found on B cells, follicular dendritic cells, pharyngeal and cervical epithelial cells, some thymocytes, and some T cells that plays a role in signal transduction; expressed in hairy cell leukemia, B-cell lymphoma, and some T-cell ALL.

CD21 CR2 - a type I transmembrane protein found in the cytoplasm of pre-B cells and on the surface of mature B cells that facilitates signal transduction; expressed in patients with hairy cell leukemias and in some with B-cell lymphomas. Receptor for complement (C3d) and Epstein-Barr virus (EBV).

CD22 - a sugar binding transmembrane protein that specifically binds sialic acid with an immunoglobulin (Ig) domain located at its N-terminus. It is a member of the immunoglobulin superfamily and the SIGLEC family. CD22 functions as an inhibitory receptor for B cell receptor (BCR) signalling.

CD23 - a type II transmembrane protein found on mature B cells, monocytes, activated macrophages, eosinophils, platelets, and dendritic cells that enhances capture and processing of antigen complexed with IgE.

CD24 - a glycoprotein expressed at the surface of most B lymphocytes and differentiating neuroblasts. This gene encodes a sialoglycoprotein that is expressed on mature granulocytes and in many B cells. The encoded protein is anchored via a glycosyl phosphatidylinositol (GPI) link to the cell surface.

CD25 - a type I transmembrane protein present on activated T cells, activated B cells, some thymocytes, myeloid precursors, and oligodendrocytes that associates with CD122 to form a heterodimer that can act as a high-affinity receptor for IL-2; 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. Present on the surface of resting 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.

CD28 - present on all T-cells, and when matched with the appropriate ligand (B7 or CD80 or CD86), it has costimulatory effect on the T-cell. CD28 is also expressed on eosinophil granulocytes, especially after tissue infiltration.

CD29 - integrin beta-1 - a cell adhesion molecule.

CD30 - a type I transmembrane protein present on activated T and B cells that may play a role in cell activation and/or differentiation; expressed in Hodgkin disease, some T-cell lymphomas, and anaplastic large cell lymphomas. CD30 is a member of the TNFRSF.

CD31 - PECAM-1, a cell adhesion molecule on platelets and endothelial cells.

CD32 - FcγRII, a receptor for the Fc (constant) region of immunoglobulin G (IgG). Downregulats IgG.

CD33 - found on immature myeloid cells, including acute myeloid leukemia blasts and mature monocytes.

CD34 - stem cell marker, adhesion, found on hematopoietic precursors (high concentrations in umbilical cord blood), capillary endothelium, and embryonic fibroblasts. CD34 is the defining marker of stem cells.

CD35 - Complement receptor 1 (C3b/C4b receptor).

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 costimulatory 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 lead to hyperIgM syndromes.

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, 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.

CD46 - Inhibitory complement receptor which is ubiquitously expressed on human cells.

CD47 - Membrane protein, which is involved in the increase in intracellular calcium concentration that occurs upon cell adhesion to extracellular matrix.

CD49b - Very late antigen (VLA) alpha 2 chain; found on platelets and activated B and T cells.

CD49c - Very late antigen (VLA) alpha 3 chain; found on nonhematopoietic bone marrow cells. Receptor for collagen, laminin, fibronectin, and thrombospondin.

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): facilitates adhesion between leukocytes to endothelial cells during the immune and inflammatory responses.

CD55 - Complement Decay-Accelerating Factor (DAF): regulatory factor in one of the three pathways of the immune system complement cascade.

CD56 - NCAM (neural cell adhesion molecule), a marker for natural killer cells and some T-lymphocytes.

CD58 - 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 ot Membrane attack complex inhibition factor (MACIF); MAC-inhibitory protein (MAC-IP). CD59 inhibits MAC which consists of C5-9 (mnemonic).

CD61 - Integrin beta 3 (Itgb3); Glycoprotein IIIa (GPIIIa): fibrinogen receptor; major role is in platelet aggregation. Defects in Itgb3 are causative for Glanzmann's thrombasthenia.

CD62E - E-selectin is a cell adhesion molecule expressed only on Endothelial cells activated by cytokines.

CD62L - L-selectin is a cell adhesion molecule found on Leukocytes.

CD62P - P-selectin is a cell adhesion molecule (CAM) found in granules in endothelial cells (cells lining blood vessels) and activated Platelets.

CD66 - CEA, a cell adhesion molecule (CAM) of the immunoglobulin 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-cell - 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.

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.

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).

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; Alpha 4 beta 1 ligand. Adhesion molecule involved in white blood cell migration.

CD120 - a member of the TNFRSF (like CD27, CD30, CD40, FAS).

CD127 - the 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). Expressed in CD4+ T Lymphocytes but also found in some B Lymphocytes. Binds to CD80 and CD86 receptors with a higher affinity than CD28, and inhibits T cell activation.

CD154 (CD40L) - The ligand for CD40. This is a costimulatory molecule that plays many roles, best known for activating B cells but also known to induce the activation of an APC in association with T cell receptor stimulation by MHC molecules on the APC.

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).

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.

Published: 12/15/2007
Updated: 11/17/2009