CD4

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CD4

CD4 (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 leukocytes. CD molecules can act in numerous ways, often acting as receptor or ligand important to the cell....
4) is a glycoprotein

Glycoprotein

Not to be confused with peptidoglycan or proteoglycan.Glycoproteins are proteins that contain oligosaccharide chains covalently attached to their Peptide side-chains....
expressed on the surface of T helper cells, regulatory T cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 (after the OKT4 monoclonal antibody that reacted with it) before being named CD4 in 1984. In humans, the CD4 protein is encoded by the CD4 gene

Gene

A gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cell and pass genetic trait to offspring....
.

is a co-receptor

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 a biological process, such as entry of a pathogen into a host cell....
that assists 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, in general, responsible for recognizing antigens bound to major histocompatibility complex molecules....
(TCR) to activate its T cell following an interaction with an antigen presenting cell.

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Encyclopedia

CD4 (cluster of differentiation

Cluster of differentiation

Glycoprotein

Gene

A gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cell and pass genetic trait to offspring....
.

Function

CD4 is a co-receptor

Co-receptor

T cell receptor

Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
, known as the tyrosine kinase

Tyrosine kinase

A tyrosine kinase is an enzyme that can transfer a phosphate group from Adenosine triphosphate to a tyrosine residue in a protein. Tyrosine kinases are a subgroup of the larger class of protein kinases....
lck

Lck

Lck is a protein that is found inside specialized Cell of the immune system called lymphocytes. Lck is a tyrosine kinase, which phosphorylates tyrosine residues of certain proteins involved in the intracellular signaling pathways of these lymphocytes....
, which is essential for activating many molecules involved in the signaling cascade of an activated T cell. CD4 also interacts directly with MHC class II

MHC class II

MHC Class II molecules are found only on a few specialized cell types, including macrophages, dendritic cells and B cells, all of which are professional antigen-presenting cells ....
molecules on the surface of the antigen presenting cell using its 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....
domain.

Structure

Like many cell surface receptors/markers, CD4 is a member of the immunoglobulin superfamily

Immunoglobulin superfamily

The immunoglobulin superfamily is a large group of cell surface and soluble proteins that are involved in the recognition, binding, or cell adhesion processes of Cell ....
.

It has four immunoglobulin domains (D₁ to D₄) that are exposed on the extracellular surface of the cell:

D₁ and D₃ resemble immunoglobulin variable (IgV) domains.
D₂ and D₄ resemble immunoglobulin constant (IgC) domains.

CD4 uses its D₁ domain to interact with the ß₂-domain of MHC class II molecules. T cells expressing CD4 molecules (and not CD8

CD8

CD8 is a transmembrane protein glycoprotein that serves as a co-receptor for the T cell receptor . Like the TCR, CD8 binds to a major histocompatibility complex molecule, but is specific for the major histocompatibility complex#class I MHC protein....
) on their surface, therefore, are specific for antigens presented by MHC II and not by MHC class I

MHC class I

There are two primary classes of major histocompatibility complex molecules, class I and MHC class II. MHC class I molecules are found on almost every nucleated cell of the body....
(they are MHC class II-restricted).

The short cytoplasmic/intracellular

Intracellular

Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell "....
tail (C) of CD4 contains a special sequence of amino acids that allow it to interact with the lck molecule described above.

Role in HIV infection

CD4 is a primary receptor used by HIV-1 to gain entry into host T cells.

HIV-1 attaches to CD4 with a protein in its viral envelope

Viral envelope

Many viruses have viral envelopes covering their protein capsids. The envelopes are typically derived from portions of the host cell membranes , but include some viral glycoproteins....
known as gp120

Gp120

gp120 is a glycoprotein exposed on the surface of the HIV structure and genome. The 120 in its name comes from its molecular weight of 120 Dalton ....
. The binding to CD4 creates a shift in the conformation of gp120 allowing HIV-1 to bind to two other surface receptors on the host cell, the chemokine receptors CCR5

CCR5

CCR5, short for chemokine receptor 5 is a protein which in humans is encoded by the CCR5 gene which is located on chromosome 3 on the short arm at position 21....
or CXCR4

CXCR4

CXCR4, , also called fusin, is an alpha-chemokine receptor specific for stromal-derived-factor-1 , a molecule endowed with potent chemotactic activity for lymphocytes....
, depending on whether HIV is infecting a macrophage or T-helper cell. Following a structural change in another viral protein (gp41

Gp41

gp41 is a glycoprotein non-covalent bond-bound to gp120, and provides the second step by which viral entry the cell. It is originally buried within the virus envelope, but, when gp120 binds to a CD4 receptor, gp120 changes its Conformational isomerism, causing gp41 to become exposed, where it can assist in fusion with the host cell....
), HIV inserts a fusion peptide into the host cell that allows the outer membrane of the virus to fuse with the cell membrane

Cell membrane

The cell membrane is the interface between the cellular machinery inside the cell and the fluid outside.It is a semipermeable lipid bilayer found in all cell ....
.

HIV infection leads to a progressive reduction in the number of T cells possessing CD4 receptors. Therefore, medical professionals refer to the CD4 count to decide when to begin treatment for HIV-infected patients. Normal blood values are more than 1 x10⁹/L.

Role in HIV treatments

CD4 tests measure the number of T cells containing the CD4 receptor. Results are usually expressed in the number of cells per microliter (or mm) of blood. While CD4 tests are not an HIV test in that they do not check the presence of viral DNA, or specific antibodies, they are used to assess the immune system of patients. Patients often undergo treatments when the CD4 count reaches a low point, around 200 cells per microliter. Medical professionals also refer to CD4 tests to determine the efficacy of the treatment.

CD4

Function

Structure

Role in HIV infection

Role in HIV treatments

Blood content

Further reading