CD4 molecule
PDB rendering based on 1cdh. The Protein Data Bank ( PDB) is a repository for 3-D structural data of Proteins and Nucleic acids These data typically obtained by X-ray crystallography
Available structures: 1cdh, 1cdi, 1cdj, 1cdu, 1cdy, 1g9m, 1g9n, 1gc1, 1jl4, 1q68, 1rzj, 1rzk, 1wio, 1wip, 1wiq, 2b4c, 2nxy, 2nxz, 2ny0, 2ny1, 2ny2, 2ny3, 2ny4, 2ny5, 2ny6, 3cd4
Identifiers
Symbol(s)	CD4; CD4mut
External IDs	OMIM: 186940 MGI: 88335 HomoloGene: 513
RNA expression pattern
More reference expression data
Orthologs
	Human	Mouse
Entrez	920	12504
Ensembl	ENSG00000010610	ENSMUSG00000023274
Uniprot	P01730	O55054
Refseq	NM_000616 (mRNA) NP_000607 (protein)	NM_013488 (mRNA) NP_038516 (protein)
Location	Chr 12: 6.77 - 6.8 Mb	Chr 6: 124.83 - 124.85 Mb
Pubmed search	[1]	[2]

CD4 (cluster of differentiation 4) is a glycoprotein expressed on the surface of T helper cells, regulatory T cells, monocytes, macrophages, and dendritic cells. The cluster of differentiation (often abbreviated as CD) is a protocol used for the identification and investigation of Cell surface molecules present on Leukocytes Not to be confused with Peptidoglycan. Glycoproteins are proteins that contain Oligosaccharide chains ( Glycans) covalently attached T helper cells (also known as effector T cells or Th cells) are a sub-group of Lymphocytes (a type of White blood cell or Regulatory T cells (sometimes known as suppressor T cells) are a specialized subpopulation of T cells that act to suppress activation of the Immune system Monocyte is a type of Leukocyte, part of the Human body 's Immune system. Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that Dendritic cells (DCs are Immune cells and form part of the Mammalian Immune system. 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. ^[1]

Contents 1 Function 2 Structure 3 Role in HIV infection 4 Role in HIV treatments 5 Notes 6 References

Function

On T cells, CD4 is a co-receptor that assists the T cell receptor (TCR) to activate its T cell following an interaction with an antigen presenting cell. T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity. 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 The T cell receptor or TCR is a molecule found on the surface of T lymphocytes (or T cells that is in general responsible for recognizing Antigens bound See also Antigen presentation An antigen-presenting cell ( APC) or accessory cell is a cell that displays foreign Antigen complexed Using its portion that resides inside the T cell, CD4 amplifies the signal generated by the TCR by recruiting an enzyme, known as the tyrosine kinase lck, which is essential for activating many molecules involved in the signaling cascade of an activated T cell. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins A tyrosine kinase is an Enzyme that can transfer a Phosphate group from ATP to a Tyrosine residue in a Protein. Lck (or leukocyte-specific protein tyrosine kinase) is a Protein that is found inside specialized cells of the Immune system called CD4 also interacts directly with MHC class II molecules on the surface of the antigen presenting cell using its extracellular domain. MHC ( Major histocompatibility complex) Class II molecules are found only on a few specialized cell types including Macrophages Dendritic cells and In Cell biology, Molecular biology and related fields the word extracellular (or sometimes extracellular space) means "outside the cell

Structure

Like many cell surface receptors/markers, CD4 is a member of the immunoglobulin superfamily. The immunoglobulin superfamily (IgSF is a large group of cell surface and soluble proteins that are involved in the recognition binding or adhesion processes of cells

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. In Cell biology, Molecular biology and related fields the word extracellular (or sometimes extracellular space) means "outside the cell Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily
• D₂ and D₄ resemble immunoglobulin constant (IgC) domains.

CD4 uses its D₁ domain to interact with the β₂-domain of MHC class II molecules. MHC ( Major histocompatibility complex) Class II molecules are found only on a few specialized cell types including Macrophages Dendritic cells and T cells expressing CD4 molecules (and not CD8) on their surface, therefore, are specific for antigens presented by MHC II and not by MHC class I (they are MHC class II-restricted). CD8 ( Cluster of differentiation 8 is a transmembrane Glycoprotein that serves as a Co-receptor for the T cell receptor (TCR There are two primary classes of Major histocompatibility complex (MHC molecules class I and MHC class II.

The short cytoplasmic/intracellular tail (C) of CD4 contains a special sequence of amino acids that allow it to interact with the lck molecule described above. The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane. Not to be confused with Intercellular, meaning "between cells"

Role in HIV infection

CD4 is also a primary receptor used by HIV-1 to gain entry into host T cells. Human immunodeficiency virus ( HIV) is a Lentivirus (a member of the Retrovirus family that can lead to acquired immunodeficiency syndrome

The HIV-1 virus attaches to CD4 with a particular protein in its viral envelope known as gp120. Many Viruses (eg influenza and many animal viruses have viral envelopes covering their protein Capsids The envelopes are typically derived from portions of gp120 is a Glycoprotein exposed on the surface of the HIV envelope. The binding to CD4 creates a shift in the conformation of the viral gp120 protein allowing HIV-1 to bind to two other cell surface receptors on the host cell (the chemokine receptors CCR5 and CXCR4). Chemokine receptors are Cytokine receptors found on the surface of certain cells which interact with a type of Cytokine called a Chemokine. CCR5, short for chemokine (C-C motif receptor 5, is a Chemokine receptor. CXCR4, (a '''CXC''' chemokine '''R'''eceptor) also called fusin, is an alpha- Chemokine receptor specific for stromal-derived-factor-1 ( SDF-1 Following another change in shape of a different viral protein (gp41), HIV inserts a fusion peptide into the host T cell that allows the outer membrane of the virus to fuse with the T-cell membrane. gp41 is a Glycoprotein non- covalently -bound to gp120 and provides the second step by which HIV enters the cell The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer

HIV infection leads to a progressive reduction in the number of T cells possessing CD4 receptors and, therefore, the CD4 count is used as an indicator to help physicians decide when to begin treatment in HIV-infected patients. Normal blood values are > 1^[2] x10⁹/L. A Reference range is a set of values used by a Health professional to interpret a set of Medical test results

Role in HIV treatments

CD4 tests consist in enumerating the number of T cells containing the CD4 receptor. Result are usually expressed in cell per microliter of blood. While CD4 tests are not an HIV test (they do not look for the presence of viral DNA, or for the presence of specific Antibodies) CD4 tests are critical in assessing the immune system of patients. Treatments are often started when the CD4 count reach a low point, around ~200 cells per microliter. CD4 tests are also used to judge treatment efficacy.

Notes

References

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