CD4 Products

Description

CD4 (cluster of differentiation 4), also known as L3T4 or T4, is a 55 kDa single chain type I transmembrane glycoprotein belonging to the immunoglobin (Ig) superfamily. CD4 is predominantly expressed on most thymocytes, a subset of mature T lymphocytes, and weakly on monocytes, tissue macrophages, dendritic cells, and granulocytes. It is also expressed on neurons and glial cells in the brain (1). CD4 is expressed along with CD8 on double positive T cells during their development in the thymus. Either CD4 or CD8 expression is then lost giving rise to single positive (SP) CD4+ or CD8+ mature T cells. CD4+ SP cells (T helper cells) further differentiate into multiple subsets of CD4+ cells including Th1, Th2, Th17, Tfh, and Treg cells which regulate humoral and cellular immunity (2). The extracellular region of CD4 consists of 372 amino acids (aa) with four immunoglobin-like domains (D1-D4). The structures of D1 and D3 resemble variable (IgV) domains while D2 and D4 resemble constant (IgC) domains (3).

Given its critical role in T cell development, CD4 also has diverse immunology-related functions. CD4 acts as a coreceptor with the T-cell receptor (TCR) during T cell activation and thymic differentiation by binding directly to major histocompatibility complex (MHC) class II antigens and associating with the protein tyrosine kinase, Lck (4). This interaction contributes to the formation of the immunological synapse (5). Defects in antigen presentation cause dysfunction of CD4+ T cells and the almost complete loss of MHC II expression on B cells in peripheral blood, as observed in severe combined immunodeficiency (SCID) (6). CD4 also functions as a receptor for the human immunodeficiency virus (HIV) by binding to gp120, the envelope glycoprotein of HIV-1. It has been shown that the V-like domains are critical for binding to gp120 (7). In immune mediated and infectious diseases of the central nervous system, CD4 functions as an indirect mediator of neuronal damage (8).

References

1. Omri, B., Crisanti, P., Alliot, F., Marty, M., Rutin, J., Levallois, C.,... Pessac, B. (1994). CD4 expression in neurons of the central nervous system. International Immunology, 6(3), 377-385. doi:10.1093/intimm/6.3.377

2. Wan, Y. Y., & Flavell, R. A. (2009). How diverse-CD4 effector T cells and their functions. Journal of Molecular Cell Biology, 1(1), 20-36. doi:10.1093/jmcb/mjp001

3. Wu, H., Myszka, D. G., Tendian, S. W., Brouillette, C. G., Sweet, R. W., Chaiken, I. M., & Hendrickson, W. A. (1996). Kinetic and structural analysis of mutant CD4 receptors that are defective in HIV gp120 binding. Proceedings of the National Academy of Sciences, 93(26), 15030-15035. doi:10.1073/pnas.93.26.15030

4. Doyle, C., & Strominger, J. L. (1987). Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature, 330, 256-259. doi:10.1038/330256a0

5. Vignali, D. A. (2010). CD4 on the road to coreceptor status. The Journal of Immunology, 184(11), 5933-5934. doi:10.4049/jimmunol.1090037

6. Tasher, D., & Dalal, I. (2012). The genetic basis of severe combined immunodeficiency and its variants. The Application of Clinical Genetics, 5, 67-80. doi:10.2147/tacg.s18693

7. Arthos, J., Deen, K. C., Chaikin, M. A., Fornwald, J. A., Sathe, G., Sattentau, Q. J.,... Sweet, R. W. (1989). Identification of the residues in human CD4 critical for the binding of HIV. Cell, 57(3), 469-481. doi:10.1016/0092-8674(89)90922-7

8. Buttini, M., Westland, C. E., Masliah, E., Yafeh, A. M., Wyss-Coray, T., Mucke, L. (1998). Novel role of human cd4 molecule identified in neurodegeneration. Nature Medicine, 4(4), 441-446. doi:10.1038/nm0498-441

Bioinformatics

Entrez	920 Human 12504 Mouse 24932 Rat 713807 Monkey
Uniprot	NP_000607 Human P01730 Human
Product By Gene ID	920
Alternate Names	CD_antigen: CD4 CD4 CD4mut CD4 antigen T-cell surface antigen T4/Leu-3 T-cell surface glycoprotein CD4 CD4 antigen (p55) CD4 receptor CD4 molecule

Diseases related to CD4

Discover more about diseases related to CD4.

Hiv Infections
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
Neoplasms
Autoimmune Reaction
Infective Disorder
Inflammation
Malignant Neoplasms
Autoimmune Diseases
Virus Diseases
Decreased Immunologic Activity [pe]
Aids-related Opportunistic Infections
Tuberculosis
Lymphoma
Hepatitis
Leukemia
Autoimmunity
Pneumonia

Pathways for CD4

View related products by pathway and learn more about each of the pathways below.

Immune Response
Pathogenesis
Secretion
Cell Activation
Cytokine Production
Cell Proliferation
T Cell Activation
Cell Death
Viral Replication
T Cell Proliferation
Hypersensitivity
Cell Development
Cell Differentiation
Localization
Inflammatory Response
Cytokine Secretion
Tropism
Lymphocyte Proliferation
Drug Resistance
Aging

Research Areas for CD4

Find related products by research area and learn more about each of the different research areas below.

Adaptive Immunity
CD Markers
Cell Biology
Cellular Markers
Cytokine Research
Immunology
Stem Cell Markers

PTMs for CD4

Learn more about PTMs related to CD4.

Phosphorylation
Cleavage
Glycosylation
Methylation
Acetylation
Demethylation
Reduction
Dephosphorylation
Ubiquitination
Deglycosylation
Biotinylation
Oxidation
Myristoylation
Ribosylation
Nitration
Deamidation
Deacetylation
Citrullination
Palmitoylation
Phosphorothioation

Bioinformatics Tool for CD4

Discover related pathways, diseases and genes to CD4. Need help? Read the Bioinformatics Tool Guide for instructions on using this tool.
 

Related CD4 Blog Posts

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CD4 - An Important Co-receptor Assisting TCRs The cluster of differentiation 4 (CD4) protein is a surface, type I membrane-embedded glycoprotein that is found on a wide range of cells: T-lymphocytes, B-cells, macrophages, granulocytes, and developmentally-dependent regions specific to the brain....    Read more.

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