Structure of the Interleukin-15 quaternary complex
[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.          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. 
[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.  [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.
Publication Abstract from PubMed
Interleukin 15 (IL-15) and IL-2 have distinct immunological functions even though both signal through the receptor subunit IL-2Rbeta and the common gamma-chain (gamma(c)). Here we found that in the structure of the IL-15-IL-15Ralpha-IL-2Rbeta-gamma(c) quaternary complex, IL-15 binds to IL-2Rbeta and gamma(c) in a heterodimer nearly indistinguishable from that of the IL-2-IL-2Ralpha-IL-2Rbeta-gamma(c) complex, despite their different receptor-binding chemistries. IL-15Ralpha substantially increased the affinity of IL-15 for IL-2Rbeta, and this allostery was required for IL-15 trans signaling. Consistent with their identical IL-2Rbeta-gamma(c) dimer geometries, IL-2 and IL-15 showed similar signaling properties in lymphocytes, with any differences resulting from disparate receptor affinities. Thus, IL-15 and IL-2 induced similar signals, and the cytokine specificity of IL-2Ralpha versus IL-15Ralpha determined cellular responsiveness. Our results provide new insights for the development of specific immunotherapeutics based on IL-15 or IL-2.
Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-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 Nat Immunol. 2012 Oct 28. doi: 10.1038/ni.2449. PMID:23104097
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.