4gs7

Structural highlights

Disease

[IL2RG_HUMAN] Defects in IL2RG are the cause of severe combined immunodeficiency X-linked T-cell-negative/B-cell-positive/NK-cell-negative (XSCID) [MIM:300400]; also known as agammaglobulinemia Swiss type. A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]} Defects in IL2RG are the cause of X-linked combined immunodeficiency (XCID) [MIM:312863]. XCID is a less severe form of X-linked immunodeficiency with a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID.^{[11] [12]}

Function

[I15RA_HUMAN] High-affinity receptor for interleukin-15. Can signal both in cis and trans where IL15R from one subset of cells presents IL15 to neighboring IL2RG-expressing cells. Expression of different isoforms may alter or interfere with signal transduction. Isoform 5, isoform 6, isoform 7 and isoform 8 do not bind IL15. Signal transduction involves STAT3, STAT5, STAT6, JAK2 (By similarity) and SYK.^{[13] [14]} [IL15_HUMAN] Cytokine that stimulates the proliferation of T-lymphocytes. Stimulation by IL-15 requires interaction of IL-15 with components of IL-2R, including IL-2R beta and probably IL-2R gamma but not IL-2R alpha. [IL2RG_HUMAN] Common subunit for the receptors for a variety of interleukins. [IL2RB_HUMAN] Receptor for interleukin-2. This beta subunit is involved in receptor mediated endocytosis and transduces the mitogenic signals of IL2.

See Also

• Interleukin
• Interleukin receptor

References

1. ↑ Puck JM, Deschenes SM, Porter JC, Dutra AS, Brown CJ, Willard HF, Henthorn PS. The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1. Hum Mol Genet. 1993 Aug;2(8):1099-104. PMID:8401490
2. ↑ DiSanto JP, Dautry-Varsat A, Certain S, Fischer A, de Saint Basile G. Interleukin-2 (IL-2) receptor gamma chain mutations in X-linked severe combined immunodeficiency disease result in the loss of high-affinity IL-2 receptor binding. Eur J Immunol. 1994 Feb;24(2):475-9. PMID:8299698
3. ↑ Markiewicz S, Subtil A, Dautry-Varsat A, Fischer A, de Saint Basile G. Detection of three nonsense mutations and one missense mutation in the interleukin-2 receptor gamma chain gene in SCIDX1 that differently affect the mRNA processing. Genomics. 1994 May 1;21(1):291-3. PMID:8088810 doi:http://dx.doi.org/10.1006/geno.1994.1265
4. ↑ Ishii N, Asao H, Kimura Y, Takeshita T, Nakamura M, Tsuchiya S, Konno T, Maeda M, Uchiyama T, Sugamura K. Impairment of ligand binding and growth signaling of mutant IL-2 receptor gamma-chains in patients with X-linked severe combined immunodeficiency. J Immunol. 1994 Aug 1;153(3):1310-7. PMID:8027558
5. ↑ DiSanto JP, Rieux-Laucat F, Dautry-Varsat A, Fischer A, de Saint Basile G. Defective human interleukin 2 receptor gamma chain in an atypical X chromosome-linked severe combined immunodeficiency with peripheral T cells. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9466-70. PMID:7937790
6. ↑ Pepper AE, Buckley RH, Small TN, Puck JM. Two mutational hotspots in the interleukin-2 receptor gamma chain gene causing human X-linked severe combined immunodeficiency. Am J Hum Genet. 1995 Sep;57(3):564-71. PMID:7668284
7. ↑ Clark PA, Lester T, Genet S, Jones AM, Hendriks R, Levinsky RJ, Kinnon C. Screening for mutations causing X-linked severe combined immunodeficiency in the IL-2R gamma chain gene by single-strand conformation polymorphism analysis. Hum Genet. 1995 Oct;96(4):427-32. PMID:7557965
8. ↑ Puck JM, Pepper AE, Bedard PM, Laframboise R. Female germ line mosaicism as the origin of a unique IL-2 receptor gamma-chain mutation causing X-linked severe combined immunodeficiency. J Clin Invest. 1995 Feb;95(2):895-9. PMID:7860773 doi:http://dx.doi.org/10.1172/JCI117740
9. ↑ Stephan V, Wahn V, Le Deist F, Dirksen U, Broker B, Muller-Fleckenstein I, Horneff G, Schroten H, Fischer A, de Saint Basile G. Atypical X-linked severe combined immunodeficiency due to possible spontaneous reversion of the genetic defect in T cells. N Engl J Med. 1996 Nov 21;335(21):1563-7. PMID:8900089 doi:10.1056/NEJM199611213352104
10. ↑ Jones AM, Clark PA, Katz F, Genet S, McMahon C, Alterman L, Cant A, Kinnon C. B-cell-negative severe combined immunodeficiency associated with a common gamma chain mutation. Hum Genet. 1997 May;99(5):677-80. PMID:9150740
11. ↑ Schmalstieg FC, Leonard WJ, Noguchi M, Berg M, Rudloff HE, Denney RM, Dave SK, Brooks EG, Goldman AS. Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency. J Clin Invest. 1995 Mar;95(3):1169-73. PMID:7883965 doi:http://dx.doi.org/10.1172/JCI117765
12. ↑ Sharfe N, Shahar M, Roifman CM. An interleukin-2 receptor gamma chain mutation with normal thymus morphology. J Clin Invest. 1997 Dec 15;100(12):3036-43. PMID:9399950 doi:10.1172/JCI119858
13. ↑ Anderson DM, Kumaki S, Ahdieh M, Bertles J, Tometsko M, Loomis A, Giri J, Copeland NG, Gilbert DJ, Jenkins NA, et al.. Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genes. J Biol Chem. 1995 Dec 15;270(50):29862-9. PMID:8530383
14. ↑ Bulanova E, Budagian V, Pohl T, Krause H, Durkop H, Paus R, Bulfone-Paus S. The IL-15R alpha chain signals through association with Syk in human B cells. J Immunol. 2001 Dec 1;167(11):6292-302. PMID:11714793
15. ↑ Ring AM, Lin JX, Feng D, Mitra S, Rickert M, Bowman GR, Pande VS, Li P, Moraga I, Spolski R, Ozkan E, Leonard WJ, Garcia KC. Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15. Nat Immunol. 2012 Oct 28. doi: 10.1038/ni.2449. PMID:23104097 doi:http://dx.doi.org/10.1038/ni.2449