This article may be too technical for most readers to understand. Please help improve this article to make it understandable to non-experts, without removing the technical details. The talk page may contain suggestions. (March 2012)

CD4 molecule
250px Crystallographic structure of the V-set and C2 domains of human CD4.[1]
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1CDH, 1CDI, 1CDJ, 1CDU, 1CDY, 1G9M, 1G9N, 1GC1, 1JL4, 1Q68, 1RZJ, 1RZK, 1WBR, 1WIO, 1WIP, 1WIQ, 2B4C, 2JKR, 2JKT, 2KLU, 2NXY, 2NXZ, 2NY0, 2NY1, 2NY2, 2NY3, 2NY4, 2NY5, 2NY6, 2QAD, 3B71, 3CD4, 3JWD, 3JWO, 3LQA, 3O2D, 3S4S, 3S5L, 3T0E
Identifiers
Symbols	CD4; CD4mut
External IDs	OMIM: 186940 MGI: 88335 HomoloGene: 513 ChEMBL: 2754 GeneCards: CD4 Gene
Gene Ontology Molecular function • glycoprotein binding • receptor activity • transmembrane signaling receptor activity • extracellular matrix structural constituent • protein binding • zinc ion binding • coreceptor activity • enzyme binding • protein kinase binding • MHC class II protein binding • protein homodimerization activity Cellular component • early endosome • endoplasmic reticulum lumen • endoplasmic reticulum membrane • plasma membrane • plasma membrane • external side of plasma membrane • integral to membrane • T cell receptor complex • membrane raft Biological process • cytokine production • induction by virus of host cell-cell fusion • immune response • cell adhesion • signal transduction • cell surface receptor signaling pathway • enzyme linked receptor protein signaling pathway • transmembrane receptor protein tyrosine kinase signaling pathway • viral reproduction • initiation of viral infection • T cell differentiation • entry into host cell • T cell costimulation • maintenance of protein location in cell • interspecies interaction between organisms • T cell selection • positive regulation of interleukin-2 biosynthetic process • innate immune response • protein palmitoleylation • positive regulation of protein kinase activity • regulation of defense response to virus by virus • positive regulation of peptidyl-tyrosine phosphorylation • positive regulation of calcium-mediated signaling • T cell receptor signaling pathway • regulation of T cell activation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	920	12504
Ensembl	ENSG00000010610	ENSMUSG00000023274
UniProt	P01730	P06332
RefSeq (mRNA)	NM_000616.4	NM_013488.2
RefSeq (protein)	NP_000607.1	NP_038516.1
Location (UCSC)	Chr 12: 6.9 – 6.93 Mb	Chr 6: 124.81 – 124.84 Mb
PubMed search	[1]	[2]
This box: view talk edit

CD4, extracellular

structure of t-cell surface glycoprotein cd4, monoclinic crystal form
Identifiers
Symbol	CD4-extracel
Pfam	PF09191
InterPro	IPR015274
SCOP	1cid
SUPERFAMILY	1cid
OPM superfamily	230
OPM protein	2klu
CDD	cd07695
Available protein structures: Pfam structures PDB RCSB PDB; PDBe PDBsum structure summary

CD4 (cluster of differentiation 4) is a glycoprotein expressed on the surface of T helper 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.^[2] In humans, the CD4 protein is encoded by the CD4 gene.^[3][4]

Structure[link]

Schematic representation of CD4 receptor.

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

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 β₂-domain of MHC class II molecules. 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).

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.

Function[link]

CD4 is a co-receptor that assists the T cell receptor (TCR) with an antigen-presenting cell. 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. CD4 also interacts directly with MHC class II molecules on the surface of the antigen-presenting cell using its extracellular domain. The extracellular domain adopts an immunoglobulin-like beta-sandwich with seven strands in 2 beta sheets, in a Greek key topology.^[5]

Other Interactions[link]

CD4 has also been shown to interact with SPG21,^[6] Lck^{[7][8][9][10][11]} and Protein unc-119 homolog.^[12]

Disease[link]

HIV infection[link]

HIV-1 uses CD4 to gain entry into host T-cells and achieves this by binding of the viral envelope protein known as gp120 to CD4.^[13] The binding to CD4 creates a shift in the conformation of gp120 allowing HIV-1 to bind to a co-receptor expressed on the host cell. These co-receptors are chemokine receptors CCR5 or CXCR4, which of these co-receptor is used during infection is dependent on whether the virus is infecting a macrophage or T-helper cell^{[citation needed]}. Following a structural change in another viral protein (gp41), HIV inserts a fusion peptide into the host cell that allows the outer membrane of the virus to fuse with the cell membrane.

HIV pathology[link]

HIV infection leads to a progressive reduction in the number of T cells expressing CD4. Medical professionals refer to the CD4 count to decide when to begin treatment during HIV infection. Normal blood values are 500-1200x10⁶/L.^[14] CD4 count test measures the number of T cells expressing CD4. Results are usually expressed in the number of cells per microliter (or cubic millimeter, mm³) of blood. While CD4 tests are not a direct HIV test e.g. does not check the presence of viral DNA, or specific antibodies against HIV, the CD4 count is used to assess the immune system of patients. Patients often undergo treatments when the CD4 count reach a level of 350 cells per microliter; less than 200 cells per microliter in an HIV positive individual is diagnosed as AIDS. Medical professionals also refer to CD4 tests to determine efficacy of treatment.

Reference ranges for blood tests of white blood cells, comparing CD4+ cell amount (shown in green-yellow) with other cells.

Other diseases[link]

CD4 continues to be expressed in most neoplasms derived from T helper cells. It is therefore possible to use CD4 immunohistochemistry on tissue biopsy samples to identify most forms of peripheral T cell lymphoma and related malignant conditions.^[15] The antigen has also been associated with a number of autoimmune diseases such as vitiligo and type I diabetes mellitus.^[16]

References[link]

Further reading[link]

External links[link]

• CD1+Antigen at the US National Library of Medicine Medical Subject Headings (MeSH)
• Mouse CD Antigen Chart
• Human CD Antigen Chart
• *Human Immunodeficiency Virus Glycoprotein 120

v t e PDB gallery 1cdh: STRUCTURES OF AN HIV AND MHC BINDING FRAGMENT FROM HUMAN CD4 AS REFINED IN TWO CRYSTAL LATTICES   1cdi: STRUCTURES OF AN HIV AND MHC BINDING FRAGMENT FROM HUMAN CD4 AS REFINED IN TWO CRYSTAL LATTICES   1cdj: STRUCTURE OF T-CELL SURFACE GLYCOPROTEIN CD4   1cdu: STRUCTURE OF T-CELL SURFACE GLYCOPROTEIN CD4 MUTANT WITH PHE 43 REPLACED BY VAL   1cdy: STRUCTURE OF T-CELL SURFACE GLYCOPROTEIN CD4 MUTANT WITH GLY 47 REPLACED BY SER   1g9m: HIV-1 HXBC2 GP120 ENVELOPE GLYCOPROTEIN COMPLEXED WITH CD4 AND INDUCED NEUTRALIZING ANTIBODY 17B   1g9n: HIV-1 YU2 GP120 ENVELOPE GLYCOPROTEIN COMPLEXED WITH CD4 AND INDUCED NEUTRALIZING ANTIBODY 17B   1gc1: HIV-1 GP120 CORE COMPLEXED WITH CD4 AND A NEUTRALIZING HUMAN ANTIBODY   1jl4: CRYSTAL STRUCTURE OF THE HUMAN CD4 N-TERMINAL TWO DOMAIN FRAGMENT COMPLEXED TO A CLASS II MHC MOLECULE   1q68: Solution structure of T-cell surface glycoprotein CD4 and Proto-oncogene tyrosine-protein kinase LCK fragments   1rzj: HIV-1 HXBC2 GP120 ENVELOPE GLYCOPROTEIN COMPLEXED WITH CD4 AND INDUCED NEUTRALIZING ANTIBODY 17B   1rzk: HIV-1 YU2 GP120 ENVELOPE GLYCOPROTEIN COMPLEXED WITH CD4 AND INDUCED NEUTRALIZING ANTIBODY 17B   1wio: STRUCTURE OF T-CELL SURFACE GLYCOPROTEIN CD4, TETRAGONAL CRYSTAL FORM   1wip: STRUCTURE OF T-CELL SURFACE GLYCOPROTEIN CD4, MONOCLINIC CRYSTAL FORM   1wiq: STRUCTURE OF T-CELL SURFACE GLYCOPROTEIN CD4, TRIGONAL CRYSTAL FORM   2b4c: Crystal structure of HIV-1 JR-FL gp120 core protein containing the third variable region (V3) complexed with CD4 and the X5 antibody   2nxy: HIV-1 gp120 Envelope Glycoprotein(S334A) Complexed with CD4 and Antibody 17b   2nxz: HIV-1 gp120 Envelope Glycoprotein (T257S, S334A, S375W) Complexed with CD4 and Antibody 17b   2ny0: HIV-1 gp120 Envelope Glycoprotein (M95W, W96C, T257S, V275C, S334A, S375W, A433M) Complexed with CD4 and Antibody 17b   2ny1: HIV-1 gp120 Envelope Glycoprotein (I109C, T257S, S334A, S375W, Q428C) Complexed with CD4 and Antibody 17b   2ny2: HIV-1 gp120 Envelope Glycoprotein (T123C, T257S, S334A, S375W, G431C) Complexed with CD4 and Antibody 17b   2ny3: HIV-1 gp120 Envelope Glycoprotein (K231C, T257S, E267C, S334A, S375W) Complexed with CD4 and Antibody 17b   2ny4: HIV-1 gp120 Envelope Glycoprotein (K231C, T257S, E268C, S334A, S375W) Complexed with CD4 and Antibody 17b   2ny5: HIV-1 gp120 Envelope Glycoprotein (M95W, W96C, I109C, T257S, V275C, S334A, S375W, Q428C, A433M) Complexed with CD4 and Antibody 17b   2ny6: HIV-1 gp120 Envelope Glycoprotein (M95W, W96C, I109C, T123C, T257S, V275C,S334A, S375W, Q428C, G431C) Complexed with CD4 and Antibody 17b   3cd4: REFINEMENT AND ANALYSIS OF THE FIRST TWO DOMAINS OF HUMAN CD4

This article incorporates text from the public domain Pfam and InterPro IPR015274

Fernando Rocha (born 1975) is a Portuguese comedian, actor, and TV presenter, whose career as a professional performer began in 2000. He has performed in Portugal, and internationally, including Angola, which has a majority Portuguese speaking population.

References[link]

• "Promoter Zona Jovem holds big show of humour", Angola Press, July 28, 2009
• "Cine Atlantico records high turnout for humorist Fernando Rocha", Angola Press, August 10, 2009
• Rocha and Association Football at worldsoccerbars.com
• “A Minha Vida Numa Anedota” (biography of Rocha), Natacha Lima Reis. Prime Books, 2006 (in Portuguese)

External links[link]

• Rocha website (in Portuguese)