CD8 (

cluster of differentiation The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophen ...

8) is a

transmembrane A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequent ...

glycoprotein that serves as a

co-receptor A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to facilitate ligand recognition and initiate biological processes, such as entry of a pathogen into a host cell. Properties The ...

for the

T-cell receptor The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding b ...

(TCR). Along with the TCR, the CD8 co-receptor plays a role in T cell signaling and aiding with cytotoxic T cell-

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...

interactions. Like the TCR, CD8 binds to a major histocompatibility complex (MHC) molecule, but is specific for the MHC class I protein. There are two

isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some iso ...

of the protein, alpha and beta, each encoded by a different gene. In humans, both genes are located on

chromosome 2 Chromosome 2 is one of the twenty-three pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 2 is the second-largest human chromosome, spanning more than 242 million base pairs and representing almost e ...

in position 2p12.

Tissue distribution

The CD8 co-receptor is predominantly expressed on the surface of cytotoxic T cells, but can also be found on natural killer cells, cortical

thymocyte A Thymocyte is an immune cell present in the thymus, before it undergoes transformation into a T cell. Thymocytes are produced as stem cells in the bone marrow and reach the thymus via the blood. Thymopoiesis describes the process which turns thymo ...

s, and dendritic cells. The CD8 molecule is a marker for cytotoxic T cell population. It is expressed in T cell lymphoblastic lymphoma and hypo-pigmented

mycosis fungoides Mycosis fungoides, also known as Alibert-Bazin syndrome or granuloma fungoides, is the most common form of cutaneous T-cell lymphoma. It generally affects the skin, but may progress internally over time. Symptoms include rash, tumors, skin lesion ...

Structure

To function, CD8 forms a dimer, consisting of a pair of CD8 chains. The most common form of CD8 is composed of a CD8-α and CD8-β chain, both members of the

immunoglobulin superfamily The immunoglobulin superfamily (IgSF) is a large protein superfamily 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 ...

with an immunoglobulin variable (IgV)-like extracellular domain connected to the membrane by a thin stalk, and an intracellular tail. Less-common

homodimer In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...

s of the CD8-α chain are also expressed on some cells. The molecular weight of each CD8 chain is about 34 kDa. The structure of the CD8 molecule was determined by Leahy, D.J., Axel, R., and Hendrickson, W.A. by X-ray Diffraction at a 2.6A resolution.; The structure was determined to have an immunoglobulin-like beta-sandwich folding and 114 amino acid residues. 2% of the protein is wound into α-helices and 46% into β-sheets, with the remaining 52% of the molecules remaining in the loop portions. CD8 receptor

Function

The extracellular IgV-like domain of CD8-α interacts with the α₃ portion of the Class I MHC molecule. This affinity keeps the

T cell receptor The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding ...

of the cytotoxic T cell and the target cell bound closely together during antigen-specific activation. Cytotoxic T cells with CD8 surface protein are called CD8+ T cells. The main recognition site is a flexible loop at the α₃ domain of an MHC molecule. This was discovered by doing mutational analyses. The flexible α₃ domain is located between residues 223 and 229 in the genome. In addition to aiding with cytotoxic T cell antigen interactions the CD8 co-receptor also plays a role in T cell signaling. The cytoplasmic tails of the CD8 co-receptor interact with Lck (lymphocyte-specific protein tyrosine kinase). Once the T cell receptor binds its specific antigen Lck phosphorylates the cytoplasmic CD3 and ζ-chains of the TCR complex which initiates a cascade of phosphorylation eventually leading to activation of transcription factors like NFAT, NF-κB, and AP-1 which affect the expression of certain genes.

References

External links

T-cell Group - Cardiff University

* CD8 alpha - Marker for cytotoxic T lymphocytes {{Clusters of differentiation by lineage Clusters of differentiation Immunology T cells