WordNet

a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response
any of several lymphokines that promote macrophages and killer T cells and B cells and other components of the immune system

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=sense organ / 受信装置

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/10/20 23:06:18」(JST)

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The interleukin-2 receptor (IL-2R) is a heterotrimeric protein expressed on the surface of certain immune cells, such as lymphocytes, that binds and responds to a cytokine called IL-2.

Composition

IL-2 binds to the IL-2 receptor, which has three forms, generated by different combinations of three different proteins, often referred to as "chains": α (alpha) (also called IL-2Rα, CD25, or Tac antigen), β (beta) (also called IL-2Rβ, or CD122), and γ (gamma) (also called IL-2Rγ, γ_c, common gamma chain, or CD132); these subunits are also parts of receptors for other cytokines.^[1]^:713 The β and γ chains of the IL-2R are members of the type I cytokine receptor family.^[2]

Structure-activity relationships of the IL-2/IL-2R interaction

The three receptor chains are expressed separately and differently on various cell types and can assemble in different combinations and orders to generate low, intermediate, and high affinity IL-2 receptors.

The α chain binds IL-2 with low affinity, the combination of β and γ together form a complex that binds IL-2 with intermediate affinity, primarily on memory T cells and NK cells; and all three receptor chains form a complex that binds IL-2 with high affinity (Kd ~ 10−11 M) on activated T cells and regulatory T cells The intermediate and high affinity receptor forms are functional and cause changes in the cell when IL-2 binds to them.^[2]

The structure of the stable complex formed when IL-2 binds to the high affinity receptor has been determined using X-ray crystallography. The structure supports a model wherein IL-2 initially binds to the α chain, then the β is recruited, and finally γ.^[2]^[3]^[4]

Signaling

The three IL-2 receptor chains span the cell membrane and extend into the cell, thereby delivering biochemical signals to the cell interior. The alpha chain does not participate in signaling, but the beta chain is complexed with an enzyme called Janus kinase 1 (JAK1), that is capable of adding phosphate groups to molecules. Similarly the gamma chain complexes with another tyrosine kinase called JAK3. These enzymes are activated by IL-2 binding to the external domains of the IL-2R. As a consequence, three intracellular signaling pathways are initiated, the MAP kinase pathway, the Phosphoinositide 3-kinase (PI3K) pathway, and the JAK-STAT pathway.^[2]^[3]

Once IL2 binds to the high affinity receptor, the complex is rapidly internalized and has only a short time to signal. IL-2, IL-2Rβ, and γc are rapidly degraded, but IL-2Rα is recycled to the cell surface. Thus, the concentration of IL-2 and its receptor available determines the tempo, magnitude and extent of T cell immune responses.^[2]^[3]

IL-2 and its receptor have key roles in key functions of the immune system, tolerance and immunity, primarily via their direct effects on T cells. In the thymus, where T cells mature, they prevent autoimmune diseases by promoting the differentiation of certain immature T cells into regulatory T cells, which kill off other T cells that are primed to attack normal healthy cells in the body. IL-2/IL2R also promotes the differentiation of T cells into effector T cells and into memory T cells when the initial T cells is also stimulated by an antigen, thus helping the body fight off infections.^[2] Through their role in the development of T cell immunologic memory, which depends upon the expansion of the number and function of antigen-selected T cell clones, they also have a key role in enduring cell-mediated immunity.^[2]^[3]

Clinical implications

Drugs that inhibit IL-2 receptors, such as basiliximab and daclizumab are used in conjunction with other drugs to prevent immune rejection of transplants.^[5]

History

According to an immunology textbook: "IL-2 is particularly important historically, as it is the first type I cytokine that was cloned, the first type I cytokine for which a receptor component was cloned, and was the first short-chain type I cytokine whose receptor structure was solved. Many general principles have been derived from studies of this cytokine, including its being the first cytokine demonstrated to act in a growth factor–like fashion through specific high-affinity receptors, analogous to the growth factors being studied by endocrinologists and biochemists".^[1]^:712

References

^ ^a ^b Warren J. Leonard. Type I Cytokines and Interferons and Their Receptors. Chapter 23 in Fundamental Immunology, 6th ed. Editor, William E. Paul. Philadelphia : Wolters Kluwer/Lippincott Williams & Wilkins, c2008. ISBN 9780781765190
^ ^a ^b ^c ^d ^e ^f ^g Liao W, Lin JX, Leonard WJ (2011). "IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation". Curr. Opin. Immunol. 23 (5): 598–604. doi:10.1016/j.coi.2011.08.003. PMC 3405730. PMID 21889323.
^ ^a ^b ^c ^d Malek TR, Castro I (2010). "Interleukin-2 receptor signaling: at the interface between tolerance and immunity". Immunity 33 (2): 153–65. doi:10.1016/j.immuni.2010.08.004. PMC 2946796. PMID 20732639.
^ Metz A, Ciglia E, Gohlke H. Modulating protein-protein interactions: from structural determinants of binding to druggability prediction to application. Curr Pharm Des. 2012;18(30):4630-47. PMID 22650257
^ Hardinger KL, Brennan DC, Klein CL. Selection of induction therapy in kidney transplantation. Transpl Int. 2013 Jul;26(7):662-72. PMID 23279211

External links

Interleukin-2 Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)

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English Journal

Inflammatory biomarkers and spontaneous preterm birth among obese women.

Wallenstein MB1, Jelliffe-Pawlowski LL2, Yang W1, Carmichael SL1, Stevenson DK1, Ryckman KK3, Shaw GM1.
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.J Matern Fetal Neonatal Med.2016 Oct;29(20):3317-22. doi: 10.3109/14767058.2015.1124083. Epub 2015 Dec 23.
OBJECTIVE: To identify associations between second-trimester serum inflammatory biomarkers and preterm birth among obese women.METHODS: In this nested case-control study, we compared 65 serum inflammatory biomarkers in obese women whose pregnancies resulted in early spontaneous preterm birth (<32
PMID 26700828

Fermented Yupingfeng polysaccharides enhance immunity by improving the foregut microflora and intestinal barrier in weaning rex rabbits.

Sun H1, Ni X1,2, Song X2, Wen B3, Zhou Y1, Zou F1, Yang M1, Peng Z1, Zhu H1, Zeng Y1, Wang H1, Fu X3, Shi Y4, Yin Z2, Pan K1, Jing B1, Zeng D5,6,7, Wang P8,9.
Applied microbiology and biotechnology.Appl Microbiol Biotechnol.2016 Sep;100(18):8105-20. doi: 10.1007/s00253-016-7619-0. Epub 2016 Jun 4.
Yupingfeng (YPF) is a kind of Astragali radix-based ancient Chinese herbal supplemented with Atractylodis Macrocephalae Rhizoma and Radix Saposhnikoviae. Increasing evidence has proven the beneficial immunomodulating activity of YPF. However, the action mechanism(s) of it is not known. Here, we expl
PMID 27260288

Subcutaneous sarcoidosis: a clinical analysis of nine patients.

Ando M1, Miyazaki E2, Hatano Y3, Nishio S4, Torigoe C4, Yamasue M4, Mukai Y4, Nureki S4, Kadota J4.
Clinical rheumatology.Clin Rheumatol.2016 Sep;35(9):2277-81. doi: 10.1007/s10067-016-3356-0. Epub 2016 Jul 23.
Subcutaneous sarcoidosis is the specific subset of cutaneous sarcoidosis frequently associated with systemic disease. However, the disease activity, severity, and prognosis have not yet been elucidated due to the limited number of reported cases. The purpose of this study was to identify the clinica
PMID 27449952

Japanese Journal

悪性リンパ腫に対する頸部リンパ節生検の術前データの有用性について

川崎泰士,和佐野浩一郎,鈴木法臣 [他],山本さゆり,小川郁
日本耳鼻咽喉科学会会報 118(3), 206-212, 2015
… 術前の ①年齢, ②性別, ③白血球数, ④リンパ球数, ⑤リンパ球 (%), ⑥好酸球 (%), ⑦単球 (%), ⑧異型リンパ球 (%), ⑨ Hb 値, ⑩ LDH 値, ⑪ CRP 値, ⑫可溶性 IL-2R 値, ⑬細胞診のデータについて悪性リンパ腫と非悪性リンパ腫で統計学的に有意差を認めるか比較検討した. …
NAID 130005065316

Similar Survival in Patients Following Heart Transplantation Receiving Induction Therapy Using Daclizumab vs. Basiliximab

, , [他], , , , , , , , , ,
Circulation Journal 79(2), 368-374, 2015
… Background:Induction therapy with interleukin-2 receptor antagonists has been established as an effective immunosuppressive strategy in the management of heart transplant (HTx) recipients. … Patients treated with daclizumab (50.3±14.7 years) were younger than those receiving basiliximab (55.8±11.2 years) or no induction therapy (54.9±14.1 years; …
NAID 130004927049

多発性脳梗塞を呈し緩徐な経過をたどった血管内大細胞型B細胞リンパ腫の1例

光武明彦,金本忠久,鈴木洋司,酒井直樹,久力権
臨床神経学 55(2), 101-106, 2015
… 経過したが，左不全片麻痺を発症し再度多発性脳梗塞と診断された．左不全片麻痺は徐々に改善したが，失調性歩行，失行症状が出現し亜急性に進行した．血液検査で乳酸脱水素酵素，可溶性インターロイキン2受容体が高値で，悪性リンパ腫をうたがった．ランダム皮膚生検，開頭脳生検を施行し，血管内にB細胞系染色陽性の異型リンパ球の集簇をみとめ，血管内大細胞型B細胞リンパ腫の診断をえた．本疾患は急速に …
NAID 130004921311

Related Pictures

★リンクテーブル★

リンク元	「CD25」「IL-2受容体」
拡張検索	「interleukin-2 receptor alpha subunit」「interleukin-2 receptor beta subunit」「soluble interleukin-2 receptor」
関連記事	「interleukin」「interleukins」

「CD25」

interleukin 2 receptor, gamma chain (severe combined immunodeficiency)
Identifiers
Symbol	IL2RG
Alt. symbols	SCIDX1, IMD4, CD132
Entrez	3561
HUGO	6010
OMIM	308380
RefSeq	NM_000206
UniProt	P31785
Other data
Locus	Chr. X q13

interleukin 2 receptor, beta chain
Identifiers
Symbol	IL2RB
Alt. symbols	CD122
Entrez	3560
HUGO	6009
OMIM	146710
RefSeq	NM_000878
UniProt	P14784
Other data
Locus	Chr. 22 q13

interleukin 2 receptor, alpha chain
Identifiers
Symbol	IL2RA
Alt. symbols	IL2R CD25
Entrez	3559
HUGO	6008
OMIM	147730
RefSeq	NM_000417
UniProt	P01589
Other data
Locus	Chr. 10 p15.1

　　[★]

同: T-cell α-chemoattractant antigen, α-chain of IL-2 receptor; インターロイキン2受容体α鎖 interleukin-2 receptor α-chain、Tac抗原 Tac antigen
関: CD, interleukin-2 receptor

概念

親和性の低いIL-2受容体はβ鎖とγ鎖からなりT細胞表面に発現している。MHC class IIと抗原複合体のTCRを介した主シグナルとB7のCD28を介した副シグナルを受けるとT細胞が活性化する。するとT細胞はCD25(α鎖)を発現し、親和性の強いIL-2受容体を形成する。IL-2はT細胞を刺激して増殖や分化を促す。 (IMM.345)