Interleukin 2
Human Interleukin 2 crystal structure
Available structures PDB 1irl, 1m47, 1m48, 1m49, 1m4a, 1m4b, 1m4c, 1nbp, 1pw6, 1py2, 1qvn, 1z92, 2b5i, 2erj, 3ink
Identifiers
Symbols	IL2; IL-2; TCGF; lymphokine
External IDs	OMIM: 147680 MGI: 96548 HomoloGene: 488 GeneCards: IL2 Gene
Gene Ontology Molecular function • cytokine activity • interleukin-2 receptor binding • kinase activator activity Cellular component • extracellular region • extracellular space Biological process • anti-apoptosis • immune response • cell adhesion • cell-cell signaling • positive regulation of cell proliferation • antimicrobial humoral response • natural killer cell activation • T cell differentiation • positive regulation of cell growth Sources: Amigo / EGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3558	16183
Ensembl	ENSG00000109471	n/a
UniProt	P60568	n/a
RefSeq (mRNA)	NM_000586	NM_008366
RefSeq (protein)	NP_000577	NP_032392
Location (UCSC)	Chr 4: 123.59 - 123.6 Mb	n/a
PubMed search	[1]	[2]

Interleukin-2 (IL-2) is an interleukin, a type of cytokine immune system signaling molecule, which is a leukocytotrophic hormone that is instrumental in the body's natural response to microbial infection and in discriminating between foreign (non-self) and self. IL-2 mediates its effects by binding to IL-2 receptors, which are expressed by lymphocytes, the cells that are responsible for immunity.

[edit] Discovery and characterization

IL-2 was the first interleukin molecule to be discovered^{[citation needed]}. The discovery of the first soluble "hormone-like" mediator of the immune system galvanized the field of immunology as the important role of cytokines had not been previously realized. A soluble factor mitogenic for lymphocytes was first found in 1965 in the culture media of mixed leukocytes and named Blastogenic Factor (BF).^[1][2] Over the next decade many similar reports appeared that described mitogenic activities in lymphocyte conditioned media. A quantitative assay for T cell Growth Factor (TCGF) was developed based upon its activity to promote the long-term proliferation of T cells in culture.^[3] Biochemical characterization of TCGF revealed it to be due to a variably glycosylated 15,500 dalton single protein molecule,^[4] and the IL-2 molecule was first purified to homogeneity by immunoaffinity chromatography by Kendall Smith and his team at Dartmouth Medical School.^[5] IL-2 was also the first cytokine shown to mediate its effects via a specific IL-2 receptor,^[6] and it was also the first interleukin to be cloned and expressed from a complementary DNA (cDNA) library.^[7] Thus, despite being designated the number 2 interleukin, it was the first interleukin molecule, receptor and gene to be discovered. It was designated number 2 because Smith's data at the time indicated that IL-1, produced by macrophages, facilitates IL-2 production by T lymphocytes (T cells).^[8][9]

[edit] IL-2 signaling pathway

Subsequently, IL-2 was discovered to be a member of a family of cytokines, which also includes IL-4, IL-7, IL-9, IL-15 and IL-21. IL-2 signals through a receptor complex consisting of IL-2 specific IL-2 receptor alpha (CD25), IL-2 receptor beta (CD122) and a common gamma chain (?c), which is shared by all members of this family of cytokines. Binding of IL-2 activates the Ras/MAPK, JAK/Stat and PI 3-kinase/Akt signaling modules. More comprehensive details are provided in NetPath.

[edit] Physiology and immunology

IL-2 is normally produced by the body during an immune response.^[10][11] When environmental substances (molecules or microbes) gain access to the body, these substances (termed antigens) are recognized as foreign by antigen receptors that are expressed on the surface of lymphocytes. Antigen binding to the T cell receptor (TCR) stimulates the secretion of IL-2, and the expression of IL-2 receptors IL-2R. The IL-2/IL-2R interaction then stimulates the growth, differentiation and survival of antigen-selected cytotoxic T cells via the activation of the expression of specific genes.^[12][13][14] As such, IL-2 is necessary for the development of T cell immunologic memory, one of the unique characteristics of the immune system, which depends upon the expansion of the number and function of antigen-selected T cell clones.

IL-2 is also necessary during T cell development in the thymus for the maturation of a unique subset of T cells that are termed regulatory T cells (T-regs).^[15][16][17] After exiting from the thymus, T-Regs function to prevent other T cells from recognizing and reacting against "self antigens", which could result in "autoimmunity". T-Regs do so by preventing the responding cells from producing IL-2^[16] Thus, IL-2 is required to discriminate between self and non-self, another one of the unique characteristics of the immune system.

IL-2 has been found to be similar to IL-15 in terms of function.^[18] Both cytokines are able to facilitate production of immunoglobulins made by B cells and induce the differentiation and proliferation of natural killer cells.^[18][19] The primary differences between IL-2 and IL-15 are found in adaptive immune responses. For example, IL-2 participates in maintenance of T-Regs and reduces self-reactive T cells. On the other hand, IL-15 is necessary for maintaining highly specific T cell responses by supporting survival of CD8 memory T cells.

[edit] Uses in medicine

The World Reference Standard for IL-2 is produced by the National Institute of Biological Standards and Control in the UK. A recombinant form of IL-2 for clinical use is manufactured by Chiron Corporation with the brand name Proleukin. It has been approved by the Food and Drug Administration (FDA) for the treatment of cancers (malignant melanoma, renal cell cancer), and is in clinical trials for the treatment of chronic viral infections, and as a booster (adjuvant) for vaccines. The use of IL-2 in HIV therapy has been found to be ineffective.

Many of the immunosuppressive drugs used in the treatment of autoimmune diseases such as corticosteroids, and organ transplant rejection (cyclosporin, tacrolimus) work by inhibiting the production of IL-2 by antigen-activated T cells. Others (sirolimus) block IL-2R signaling, thereby preventing the clonal expansion and function of antigen-selected T cells.

[edit] References

[edit] External links

• Proleukin website
• IL2 Resource Site
• IL-2 Signaling Pathway

v • d • e PDB Gallery 1irl: THE SOLUTION STRUCTURE OF THE F42A MUTANT OF HUMAN INTERLEUKIN 2   1m47: Crystal Structure of Human Interleukin-2   1m48: Crystal Structure of Human IL-2 Complexed with (R)-N-[2-[1-(Aminoiminomethyl)-3-piperidinyl]-1-oxoethyl]-4-(phenylethynyl)-L-phenylalanine methyl ester   1m49: Crystal Structure of Human Interleukin-2 Complexed with SP-1985   1m4a: Crystal Structure of Human Interleukin-2 Y31C Covalently Modified at C31 with (1H-Indol-3-yl)-(2-mercapto-ethoxyimino)-acetic acid   1m4b: Crystal Structure of Human Interleukin-2 K43C Covalently Modified at C43 with 2-[2-(2-Cyclohexyl-2-guanidino-acetylamino)-acetylamino]-N-(3-mercapto-propyl)-propionamide   1m4c: Crystal Structure of Human Interleukin-2   1nbp: Crystal Structure Of Human Interleukin-2 Y31C Covalently Modified At C31 With 3-Mercapto-1-(1,3,4,9-tetrahydro-B-carbolin-2-yl)-propan-1-one   1pw6: Low Micromolar Small Molecule Inhibitor of IL-2   1py2: Structure of a 60 nM Small Molecule Bound to a Hot Spot on IL-2   1qvn: Structure of SP4160 Bound to IL-2 V69A   1z92: structure of interleukin-2 with its alpha receptor   2b5i: cytokine receptor complex   2erj: Crystal structure of the heterotrimeric interleukin-2 receptor in complex with interleukin-2   3ink: UNRAVELING THE STRUCTURE OF INTERLEUKIN-2: REPLY

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Interleukin 2".