CD4
CD4 (cluster of differentiation 4) is a 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.[1] In humans, the CD4 protein is encoded by the CD4 gene.[2][3]
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. 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.
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 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.
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 known as gp120. 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 or CXCR4, depending on whether HIV is infecting a macrophage or T-helper cell). 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 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[4] 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 milliliter 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 milliliter. Medical professionals also refer to CD4 tests to determine the efficacy of the treatment.
Blood content
References
- ^ Alain Bernard (1984). Leucocyte typing: human leucocyte differentiation antigens detected by monoclonal antibodies: specification, classification, nomenclature: [report on the first international references workshop sponsored by INSERM, WHO and IUIS]. Berlin: Springer. pp. pages 45-48. ISBN 0-387-12056-4.
{{cite book}}:|pages=has extra text (help) - ^ Isobe M, Huebner K, Maddon PJ, Littman DR, Axel R, Croce CM (1986). "The gene encoding the T-cell surface protein T4 is located on human chromosome 12". Proc. Natl. Acad. Sci. U.S.A. 83 (12): 4399–402. PMC 323740. PMID 3086883.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Ansari-Lari MA, Muzny DM, Lu J, Lu F, Lilley CE, Spanos S, Malley T, Gibbs RA (1996). "A gene-rich cluster between the CD4 and triosephosphate isomerase genes at human chromosome 12p13". Genome Res. 6 (4): 314–26. PMID 8723724.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Fisher, Bruce; Harvey, Richard P.; Champe, Pamela C. Lippincott's Illustrated Reviews: Microbiology (Lippincott's Illustrated Reviews Series). Hagerstown, MD: Lippincott Williams & Wilkins. ISBN 0-7817-8215-5.
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