CD

CD stands for cluster of differentiation, which indicates a defined subset of cellular surface receptors (epitopes) that identify cell type and stage of differentiation, and which are recognized by antibodies.

There are more than 250 identified clusters, each a different molecule, coating the surface of B lymphocytes and T lymphocytes.

All T and B cells have about 10⁵ = 100,000 molecules on their surface. B cells are coated with CD21, CD35, CD40, and CD45 together with non-CD molecules, while T cells express CD2, CD3, CD4, CD8, CD28, CD45R, and other non-CD molecules. Many CDs are expressed on both B and T cells, including CD5, CD6, CD23, CD27, CD28, CD84. Dendritic cells also express CD4 and CD8.

▼ B lymphocyte CDs : B and T lymphocyte CDs : T lymphocyte CDs : TNFRs : CD1 : CD2 : CD3 : CD4 : CD5 : CD6 : CD8 : CD14 : CD23 : CD25 : CD27 : CD28 : CD30 : CD31 : CD36 : CD40 : CD45 : CD45 isoforms : CD55 : CD58 : CD72 : CD84 : complement CÆ : costimulatory : ITAMs : LFA : lymphocyte function associated antigen : glycoproteins : Ig superfamily : Macrophages/Monocytes : migration : pattern recognition receptors : platelets : scavenger receptors : SLAM (signaling lymphocyte activation molecule) : TNFR▼

T cell CDs:

CD2 family receptors are immunoglobulin (Ig) superfamily type I transmembrane, glycosylated proteins characterized by an N-terminal variable (V) domain that lacks disulfide bonds and a truncated Ig constant 2 (C2) domain that has two disulfide bonds in the extracellular region.

CD3 family receptors comprise three distinct chains – CD3γ, CD3δ and CD3ε in mammals – which are closely related proteins of the immunoglobulin superfamily, each containing a single extracellular immunoglobulin domain. The CD3 chains associate with TCRs and the ζ-chain to activate T lymphocytes. Together the TCR, ζ-chain, and CD3 molecules consitute the TCR complex.

The transmembrane region of the CD3 chains is negatively charged, enabling these chains to associate with the positively charged TCR chains (TCRα and TCRβ). The intracellular tails of the CD3 molecules contain a single conserved motif termed the immunoreceptor tyrosine-based activation motif (ITAM) that is essential for TCR signaling. Phosphorylation of CD3's ITAM enables the CD3 chain to bind Fyn, a membrane-associated protein tyrosine kinase important in the T cell's signaling cascade.

CD4 is notorious because of its importance in HIV/AIDs. It is an approximately 55 kDa type I membrane glycoprotein expressed predominantly on T cell precursors and a subset of mature T cells, providing the surface protein to which HIV attaches itself in order to invade the cell. CD4 is also found on the surface of monocytes, macrophages, Langerhans cells, astrocytes, keratinocytes and glial cells. The number of serum T4 cells is employed to measure the health of the immune system in people infected with HIV.[R&D]

CD8 (T8) is a protein embedded in the cell surface of 'suppressor' or regulatory T lymphocytes (Treg).

The CD31 adhesion molecule (PECAM-1) is expressed in large amounts at intercellular junctions of endothelial cells, subsets of T cells, platelets, and most other leukocytes including monocytes and neutrophils. CD31 is required for the trans-endothelial migration – extravasation – of leukocytes through intercellular junctions of vascular endothelial cells.

CD58 is also known as lymphocyte function-associated antigen (LFA-3). CD58 is a cell-bound immunoglobulin superfamily receptor with only one known ligand, which is CD2. CD58 is widely expressed on human hematopoietic and non-hematopoietic tissues, leukocytes, erythrocytes, endothelial and epithelial cells, and fibroblasts. The receptor-ligand pair, CD58 plus CD2, optimizes immune recognition and initiates T cell expansion and activation. Such contact activities can occur between helper T cells and antigen-presenting cells and between cytolytic effectors and target cells.

B and T cell CDs:

C5 is a 67 kDa surface glycoprotein of the scavenger receptor cysteine-rich (SRCR) superfamily that appears on thymocytes, mature T cells, and B cells. CD5 is important for the apoptosis of antigen-receptor induced B lymphocytes and for the maintenance of tolerance by anergic B cells. CD5 crosslinking induces extracellular mobilization of calcium ions, tyrosine phosphorylation of intracellular proteins, and production of diacylglycerol. Infection by EBV downregulates CD5 expression, while the glycoprotein is expressed in many T-cell leukemias and lymphomas.

CD6 is a member of the group B scavenger receptor cysteine-rich (SRCR) superfamily, which is expressed at low levels on immature thymocytes, at high levels on mature thymocytes, on the majority of peripheral blood T cells, a subset of B cells, and a subset of neuronal cells. Human and mouse CD6 proteins share 70% amino acid sequence identity over their full lengths.

CD23 is the receptor for the Fc portion of IgE.

CD27 Ligand/TNFSF7 is also known as CD70, and is a type II transmembrane glycoprotein belonging to the TNF superfamily (TNFSF). The expression of CD27 Ligand is induced by antigen-receptor activation in B cells. CD27/TNFRSF7 is a lymphocyte-specific member of the TNF receptor superfamily, which is expressed on a subset of human T cell precursors (thymocytes), on the majority of mature T cells, on natural killer (NK) cells, and subsets of B cells. CD27 ligation on NK cells induces proliferation and production of IFN-γ. CD27 binding (ligation) to T cells provides a co-stimulatory signal required for T cell proliferation, the promotion of effector T cell formation, and clonal expansion. The binding of CD27 to B cells inhibits the terminal differentiation of activated B cells into plasma cells and instead enhances commitment to memory B cell responses.

CD28 and CTLA-4, together with their ligands, B7-1 and B7-2, constitute one of the dominant B and T cell costimulatory pathways. CD28 and CTLA-4 are structurally homologous molecules of the immunoglobulin (Ig) gene superfamily. Mouse CD28 is expressed constitutively on almost all mouse T cells and on developing thymocytes.

CD45 is a protein tyrosine phosphatase (PTP) that regulates Src kinases required for T and B cell receptor signal transduction. CD45 dephosphorylates a negative regulatory residues on one or more of the protein tyrosine kinases that are involved in receptor-mediated second messenger formation. CD45 is located in all hematopoietic cells except erythrocytes and platelets, so it is also called the common leukocyte antigen.[]rotatable im[]

The CD45-regulated Src kinases are Lyn and Blk in B cells, and Lck and Fyn in T cells. ITAMs are immunocreceptor tyrosine bases motifs comprising two tyrosine residues separated by amino acids. RTK-phosphorylation of ITAMS enables them to bind to second family protein tyrosine kinases such as CD45, for which their SH2 domains have high binding affinity. In T cells, CD45 phosphorylates Csk, which is an inhibitory protein tyrosine kinase that controls tyrosine activity in lymphocytes. In B cells, calcium ions are transduced by the BCR, inducing CD45 expression. CD45RO, CD45RA, and CD45RB are isoforms of CD45.


CD84 is also known as Ly-9B, and is a member of the CD150/SLAM (signaling lymphocyte activation molecule) subfamily of the CD2 family (designated SLAMF5). CD84 is expressed on B cells, T cells, monocytes and platelets and acts as a self-ligand. Human and mouse CD84 share approximately 57% amino acid sequence identity.

B cell CDs:

CD40 is a type I transmembrane glycoprotein belonging to the TNF receptor superfamily. CD40 is expressed on B cells, follicular dendritic cells, dendritic cells, activated monocytes, macrophages, endothelial cells, vascular smooth muscle cells and several tumor cell lines. Human and mouse CD40s have 64% identity of amino acid sequence identity.


CD72 is a 39-43 kDa type II membrane glycoprotein of the C-type lectin family. CD72 is a pan-B cell marker that is expressed throughout the B lymphocytes differentiation (except plasma cells). CD72 is also present on follicular dendritic cells.

Monocytes/Macrophages

CD14 is a 55 kDa cell surface glycoprotein that is preferentially expressed on monocytes and macrophages. The amino acid sequence of human CD14 is approximately 65% identical to mouse CD14, and 82% identical to rat proteins.

Also: CD4, CD31 adhesion molecule (PECAM-1), CD40, CD84

Platelets:

CD36 is also known as scavenger receptor class B member 3 (SR-B3), GPIIIb, platelet membrane glycoprotein IV (GPIV), collagen receptor, thrombospondin receptor, and fatty acid translocase (FAT). CD36 is a broadly-expressed integral membrane glycoprotein with multiple physiological functions. As a member of the scavenger receptor family, CD36 is a multi-ligand pattern-recognition receptor that interacts with a large number of structurally dissimilar ligands. Upon ligand binding, CD36 transduces signals that mediate a wide range of pro-inflammatory cellular responses.

Complement CÆ activation family (RCA):

CD55, also known as decay-accelerating factor (DAF), is a 70 to 75 kDa member of the regulators of complement/CÆ activation (RCA) family of proteins. It is ubiquitously expressed on cells that are exposed to plasma complement proteins. Human CD55 is synthesized as a 381 amino acid precursor that comprises a 34 aa signal sequence, a 319 aa mature region and a 28 aa C-terminal prosegment.

Costimulatory:

CD28 and CTLA-4, together with their ligands, B7-1 and B7-2.

Pattern-recognition receptors :

CD36

Glycoproteins:

CD4, CD5, CD14, CD27, CD30, CD36, CD40, CD72

Immunoglobulin superfamily:

CD2, CD58, CD28 and CTLA-4,
CD23 is the receptor for the Fc portion of IgE.

LFA (lymphocyte function associated antigen):

CD58

migration:

CD31 adhesion molecule (PECAM-1)

Scavenger receptor (SRCR) family:

CD5, CD6, CD36

SLAM (signaling lymphocyte activation molecule) subfamily:

CD84 (Ly-9B), CD2 family (SLAMF5)


TNFRs :

CD30/TNFRSF8 is a type I transmembrane glycoprotein belonging to the TNF receptor superfamily, where the the ligand for CD30 is CD30L (CD153, TNFSF8), which is a member of the TNF superfamily. CD30 binding by CD30L mediates pleiotropic effects, including cellular proliferation, activation, differentiation, and apoptosis.

Other TNFRs are CD40 and CD27.

Miscellaneous CDs
CD9 is a member of the tetraspanin transmembrane receptor family. CD9 contains four putative transmembrane domains and two extracellular loops, and is thought to be involved in egg-sperm fusion. Several reports indicate that CD9 associates with integrins and affects cell behavior on fibronectin surfaces (ref).[s]

▲ B lymphocyte CDs : B and T lymphocyte CDs : T lymphocyte CDs : TNFRs : CD2 : CD3 : CD4 : CD5 : CD6 : CD8 : CD14 : CD23 : CD27 : CD28 : CD30 : CD31 : CD36 : CD40 : CD45 : CD45 isoforms : CD55 : CD58 : CD72 : CD84 : complement CÆ : costimulatory : ITAMs : LFA : lymphocyte function associated antigen : glycoproteins : Ig superfamily : Macrophages/Monocytes : migration : pattern recognition receptors : platelets : scavenger receptors : SLAM (signaling lymphocyte activation molecule) : TNFR ▲

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[C][CD5][CD72] Tables  Fc receptors  Immune Cytokines  Immunoglobulins


tags [Immunology][cluster+differentiation][receptor]

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surface receptors

Lymphocytes are coated with surface receptors that participate in the signaling that regulates the adaptive immune response. B lymphocytes carry antibody/ immunoglobulin BCR, while T lymphocytes carry different Ig superfamily TCR.

▼ antigen-MHC complex : BCR : cascade : CD3 : CD4 : CD8 : CD45 : common leukocyte antigen : co-receptor CD4, co-receptor CD8 : cross-linked BCR : enzymes : Fc receptors (FcR) : IgαIgβ : immunoreceptor tyrosine-based activation motifs : intracellular signal : invariant TCR chain : ITAMs : Lck : leukocyte common antigen : lymphocyte receptors : multivalent antigens : phosphorylation : phosphorylated ITAMs : protein kinases : second messengers : signal transduction complex - CD3 : signal transduction molecules : src-family protein tyrosine kinases (PTKs) : Syk : TCR : TCR-CDR3 : TCR diversity : TCR heterodimers : TCR-Ig superfamily : ZAP-70 ▼

Activation of signaling requires
● lymphocyte receptors, associated with
● ITAM-bearing signal transduction molecules, and
● CD45
● adaptor proteins
● second messengers

Signal transduction molecules:
Because both BCR and TCR have very short cytoplasmic domains they must associate with invariant signal transduction molecules in order to generate an intracellular signal (IgαIgβ for BCR, CD3 for TCR). The antigen-specific receptors and signal transduction molecules cluster together in the plasma membrane, and signaling is effected by long ITAM-containing cytoplasmic domains on the signal transduction molecules. ITAMs are immunoreceptor tyrosine-based activation motifs that are phosphorylated by src-family protein tyrosine kinase enzymes (PTK). Protein kinases add phosphate groups to tyrosine (or serine or threonine) residues of other proteins, often those of enzymes. Phosphatases remove the phosphate groups, reversing the effects of protein kinases. Phospholipases such as PLC cleave specific ester bonds in phosphoglycerides or glycerophosphatidates, converting the phospholipids into fatty acids and other lipophilic substances. Phospholipase C-γ cleaves the membrane phospholipid, phosphatidylinositol bisphosphate (PIP2 ) into the signaling molecules, inositol trisphosphate (IP3) and diacylglycerol (DAG).

Phosphorylation can activate or inactivate enzymes, or can create binding sites that lead to increased concentration of cytoplasmic proteins (and hence their accessibilty for phosphorylation). Activation of lymphocytes also requires CD45 (common leukocyte antigen), which is necessory for receptor-mediated activation of lymphocytes.

Phosphorylated ITAMs can bind to other PTKs (Syk for B cells, ZAP-70 for T cells), triggering a cascade of cytoplasmic enzymes or second messengers, such as calcium ions, diacylglycerol, G-proteins, IP3, MAP kinases, PKCs, and transcription factors. Ultimately, gene expression via transcription of mRNA leads to immune activities.

Lymphocyte receptors: BCR and TCR

BCR
Heavy chain (H) plus kappa (κ) or lambda (λ) chains.

The surfaces of B cells are coated with one of thousands of distinct Ig superfamily receptors, diversified through VDJ recombination, which bind to their cognate antigen at their antigen-binding site.

Multivalent antigens can cross-link BCR, generating signals of greater amplitude in B cells, and potentially activating the B cells to proliferate and synthesize IgM in the absence of T cell- costimulation. While B cell activation may be possible without antigen presentation, B cells are more efficiently activated by binding of BCR to an array of identical epitopes that are bound to antibody on the Fc receptors (FcR) of macrophages and neutrophils.

TCR
Alpha (α) and beta (β) or gamma (γ) and delta (δ) chains

As T cells develop in the thymus, TCR gene segments are recombined to generate diverse, unique TCRs. Only those T cells with a TCR unable to bind self-peptide on self-MHC leave the thymus for the periphery.

Antigen-specific receptors on T cells are not identical to those on B cells (BCRs). The surface receptors of T cells are members of the Ig superfamily, with Ig-like domains. Each T cell is coated with a receptor originating in a single allele, so each receptor binds with a single specificity (CDR3 for antigens and CDR1-2 for MHCs). Clonotypic monoclonal antibodies can recognize TCR idiotypes. Each Ig chain has a variable and a constant region, and CDR of variable regions define the antigen-binding specificity and framework residues.

TCR is a heterodimer composed usually of α and β chains or, in a minority, γ and δ chains. The two chains are disulfide-bonded exterior to the T cell plasma membrane in a short extended stretch of amino acids that resembles the Ig hinge region. TCR, like Ig have very short cytoplasmic tails. Both TCR chains are glycosylated at sites on their V and C regions.

Each TCR has a single CDR3 binding site for antigen, while CDR 1 and CDR 2 bind peptide antigens on MHC. CDR3 is the most variable. Binding to CD4 (on helper T cells) or CD8 (on killer T cells) activates the T cell. Antigen-binding affinity is lower than that of Ig for native (self) antigen, but binding of MHC by the T cell membrane co-receptors CD4 or CD8 increases the binding affinity of the T cell for the antigen-MHC complex.

TCR expressed on the T cell membrane along with a signal transduction complex, CD3, that is called the invariant TCR chain. CD3 molecules on all T cells are formed from identical subunits, which are composed of three dimers: gamma epsilon (γε) or delta epsilon (δε), plus either two zetas (ζζ) or a zeta/eta (ζη) heterodimer. The γ and δ chains of CD3 are not identical to the molecules found in the γd TCR.

CD4 on helper T cells is a monomeric protein with four Ig-like domains, of which the two most distal domains are thought to bind Class II MHC β2 domain. CD8 is a disulfide-linked dimer, where the a and β chains each have one Ig-like domain connected by a long extended region to the transmembrane region. CD8 binds to the α3 region of Class I MHC. The cytoplasmic tails of both CD4 and CD8 associate with a cytoplasmic tyrosine kinase, Lck, to initiate signal transduction.

ф activation ф affinity maturation ф anergy ф antibodies ф antigen ф APCs סּ apoptosis ф B cells ф CD סּ cell-cycle control סּ cell membranes ф cellular response סּ cellular signal transduction ф class-switch recombination ф clonal selection ф complement system ф costimulation ~ cytokines סּ GPCRs ф helper T cell ф immune response ф immune tolerance ф isotype switching ф killer T cells ф leukocytes ф lymphocytes ф lymphokines ф macrophages ♦ MAPKs ф MHC ф monocytes ф neutrophils ф pathogens ф pattern-recognition receptors ♦ phosphatases ♦ phospholipases ~ phospholipase C-gamma ››› phosphorylation סּ phosphotransfer-mediated signaling pathways ♦ PKCs ♦ protein kinases ~ protein tyrosine kinases (PTKs) ф receptors סּ receptor proteins סּ receptor-mediated endocytosis ♦ receptor tyrosine kinases ф secondary antibody diversification ~ second messengers ♦ serine/threonine kinases ф signaling signaling gradients ¤ signaling molecules סּ signal transduction ф somatic hypermutation ф T cells ф thymus ф VDJ recombination

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Tables  Fc receptors  Immune Cytokines  Immunoglobulins  Cell Adhesion Molecules  Cell signaling  Receptor Tyrosine Kinases (RTKs)  Receptor Signal Transduction  Second Messengers 

tags [Immunology] [BCR] [TCR] [ITAM]

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