CD4





CD4 molecule
PDB rendering based on 1cdh.
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 (glycoprotein 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 (ref: Bernard et al, editors. Leukocyte Typing. Springer-Verlag, Heidelberg. 45-48, 1984)

Function

On T cells, CD4 is the tyrosine kinase lck that is essential for activating many molecules involved in the signaling cascade of an activated T cell.

Structure

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 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.

Role in HIV infection

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

The HIV-1 virus attaches to CD4 with a particular protein in its viral envelope known as gp120. 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 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.

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.

Further reading

  • Miceli MC, Parnes JR (1993). "Role of CD4 and CD8 in T cell activation and differentiation.". Adv. Immunol. 53: 59-122. PMID 8512039.
  • Geyer M, Fackler OT, Peterlin BM (2001). "Structure--function relationships in HIV-1 Nef.". EMBO Rep. 2 (7): 580-5. doi:10.1093/embo-reports/kve141. PMID 11463741.
  • Greenway AL, Holloway G, McPhee DA, et al. (2004). "HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication.". J. Biosci. 28 (3): 323-35. PMID 12734410.
  • Bénichou S, Benmerah A (2003). "[The HIV nef and the Kaposi-sarcoma-associated virus K3/K5 proteins: "parasites"of the endocytosis pathway]". Med Sci (Paris) 19 (1): 100-6. PMID 12836198.
  • Leavitt SA, SchOn A, Klein JC, et al. (2004). "Interactions of HIV-1 proteins gp120 and Nef with cellular partners define a novel allosteric paradigm.". Curr. Protein Pept. Sci. 5 (1): 1-8. PMID 14965316.
  • Tolstrup M, Ostergaard L, Laursen AL, et al. (2004). "HIV/SIV escape from immune surveillance: focus on Nef.". Curr. HIV Res. 2 (2): 141-51. PMID 15078178.
  • Hout DR, Mulcahy ER, Pacyniak E, et al. (2005). "Vpu: a multifunctional protein that enhances the pathogenesis of human immunodeficiency virus type 1.". Curr. HIV Res. 2 (3): 255-70. PMID 15279589.
  • Joseph AM, Kumar M, Mitra D (2005). "Nef: "necessary and enforcing factor" in HIV infection.". Curr. HIV Res. 3 (1): 87-94. PMID 15638726.
  • Anderson JL, Hope TJ (2005). "HIV accessory proteins and surviving the host cell.". Current HIV/AIDS reports 1 (1): 47-53. PMID 16091223.
  • Li L, Li HS, Pauza CD, et al. (2006). "Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions.". Cell Res. 15 (11-12): 923-34. doi:10.1038/sj.cr.7290370. PMID 16354571.
  • Stove V, Verhasselt B (2006). "Modelling thymic HIV-1 Nef effects.". Curr. HIV Res. 4 (1): 57-64. PMID 16454711.
v • d • e
The MHC class II)
v • d • e
Glycoprotein 130/Oncostatin M - Leukemia inhibitory factor - common subunits (Common gamma chain, CSF2RB)

interleukin (IL22RA2) - interferon (IFNAR, IFNGR)

Other: Scavenger
v • d • e
CD283 - CD304
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "CD4". A list of authors is available in Wikipedia.