CD3 receptor
Encyclopedia
In immunology
, the CD3 T-Cell Co-Receptor (CD stands for cluster of differentiation
) is a protein complex and is composed of four distinct chains. In mammals, the complex contains a CD3γ
chain, a CD3δ
chain, and two CD3ε
chains. These chains associate with a molecule known as the T cell receptor
(TCR) and the ζ-chain to generate an activation signal in T lymphocytes. The TCR, ζ-chain and CD3 molecules together comprise the TCR complex.
containing a single extracellular
immunoglobulin domain.
The transmembrane region of the CD3 chains is negatively charged (it contains aspartate residues in the transmembrane region), a characteristic that allows these chains to associate with the positively charged TCR chains.
The intracellular tails of the CD3 molecules contain a single conserved motif known as an immunoreceptor tyrosine-based activation motif
or ITAM for short, which is essential for the signaling capacity of the TCR.
of the ITAM on CD3 renders the CD3 chain capable of binding an enzyme
called ZAP70 (zeta associated protein), a kinase
that is important in the signaling cascade of the T cell.
) that target it are being investigated as immunosuppressant
therapies (e.g., otelixizumab
) for type 1 diabetes and other autoimmune disease
s.
s from which T-cells arise in the thymus
. The pro-thymocytes differentiate into common thymocyte
s, and then into medullary thymocytes, and it is at this latter stage that CD3 antigen begins to migrate to the cell membrane. The antigen is found bound to the membranes of all mature T cells and NK cells, and in virtually no other cell type, although it does appear to be present in small amounts in Purkinje cell
s.
This high specificity, combined with the presence of CD3 at all stages of T cell development, makes it a useful immunohistochemical
marker for T cells in tissue sections. The antigen remains present in almost all T-cell lymphoma
s and leukaemias, and can therefore be used to distinguish them from superficially similar B-cell and myeloid neoplasms.
Immunology
Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. It deals with the physiological functioning of the immune system in states of both health and diseases; malfunctions of the immune system in immunological disorders ; the...
, the CD3 T-Cell Co-Receptor (CD stands for cluster of differentiation
Cluster of differentiation
The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules present on white blood cells, providing targets for immunophenotyping of cells...
) is a protein complex and is composed of four distinct chains. In mammals, the complex contains a CD3γ
CD3G
T-cell surface glycoprotein CD3 gamma chain is a protein that in humans is encoded by the CD3G gene.-Further reading:...
chain, a CD3δ
CD3D
T-cell surface glycoprotein CD3 delta chain is a protein that in humans is encoded by the CD3D gene.-Further reading:...
chain, and two CD3ε
CD3E
CD3e molecule, epsilon also known as CD3E is a polypeptide which in humans is encoded by the CD3E gene which resides on chromosome 11.- Function :...
chains. These chains associate with a molecule known as the T cell receptor
T cell receptor
The T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is responsible for recognizing antigens bound to major histocompatibility complex molecules...
(TCR) and the ζ-chain to generate an activation signal in T lymphocytes. The TCR, ζ-chain and CD3 molecules together comprise the TCR complex.
Structure
The CD3γ, CD3δ, and CD3ε chains are highly related cell surface proteins of the immunoglobulin superfamilyImmunoglobulin superfamily
The immunoglobulin superfamily is a large group of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells. Molecules are categorized as members of this superfamily based on shared structural features with immunoglobulins ; they all possess a...
containing a single extracellular
Extracellular
In cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...
immunoglobulin domain.
The transmembrane region of the CD3 chains is negatively charged (it contains aspartate residues in the transmembrane region), a characteristic that allows these chains to associate with the positively charged TCR chains.
The intracellular tails of the CD3 molecules contain a single conserved motif known as an immunoreceptor tyrosine-based activation motif
Immunoreceptor tyrosine-based activation motif
An immunoreceptor tyrosine-based activation motif is a conserved sequence of four amino acids that is repeated twice in the cytoplasmic tails of certain cell surface proteins of the immune system....
or ITAM for short, which is essential for the signaling capacity of the TCR.
Regulation
PhosphorylationPhosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
of the ITAM on CD3 renders the CD3 chain capable of binding an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
called ZAP70 (zeta associated protein), a kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
that is important in the signaling cascade of the T cell.
As a drug target
Because CD3 is required for T cell activation, drugs (often monoclonal antibodiesMonoclonal antibodies
Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell....
) that target it are being investigated as immunosuppressant
Immunosuppressant
An immunosuppressant is any substance that performs immunosuppression of the immune system. They may be either exogenous, as immunosuppressive drugs, or endogenous, as ,e. g., testosterone...
therapies (e.g., otelixizumab
Otelixizumab
Otelixizumab, also known as TRX4, is a monoclonal antibody, which is being developed for the treatment of type 1 diabetes and other autoimmune diseases. The antibody is being developed by Tolerx, Inc...
) for type 1 diabetes and other autoimmune disease
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
s.
Immunohistochemistry
CD3 is initially expressed in the cytoplasm of pro-thymocytes, the stem cellStem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
s from which T-cells arise in the thymus
Thymus
The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
. The pro-thymocytes differentiate into common thymocyte
Thymocyte
Thymocytes are hematopoietic progenitor cells present in the thymus. Thymopoiesis is the process in the thymus by which thymocytes differentiate into mature T lymphocytes. The primary function of thymocytes is the generation of T lymphocytes . The thymus provides an inductive environment, which...
s, and then into medullary thymocytes, and it is at this latter stage that CD3 antigen begins to migrate to the cell membrane. The antigen is found bound to the membranes of all mature T cells and NK cells, and in virtually no other cell type, although it does appear to be present in small amounts in Purkinje cell
Purkinje cell
For the cells of the electrical conduction system of the heart, see Purkinje fibersPurkinje cells, or Purkinje neurons , are a class of GABAergic neurons located in the cerebellar cortex...
s.
This high specificity, combined with the presence of CD3 at all stages of T cell development, makes it a useful immunohistochemical
Immunohistochemistry
Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...
marker for T cells in tissue sections. The antigen remains present in almost all T-cell lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
s and leukaemias, and can therefore be used to distinguish them from superficially similar B-cell and myeloid neoplasms.