Transcriptomics

Dataset Information

474

Mechanistic and structural insight into the functional dichotomy between interleukin-2 and interleukin-15


ABSTRACT: Interleukin-15 (IL-15) and IL-2 possess distinct immunological functions despite both signaling through IL-2Rβ and the common cytokine receptor γ-chain, γc, We find that in the IL-15/IL-15Rα/IL-2Rβ/γc quaternary complex structure, IL-15 heterodimerizes IL-2Rβ and γc identically to the IL-2/IL-2Rα/IL-2Rβ/γc complex, despite differing receptor-binding chemistries. IL-15Rα dramatically increases the affinity of IL-15 for IL-2Rβ, and this allostery is required for IL-15 trans-signaling versus IL-2 cis-signaling. Consistent with the identical IL-2Rβ/γc dimer geometry, IL-2 and IL-15 exhibited similar signaling properties in lymphocytes, with any differences resulting from disparate receptor affinities. Thus, IL-15 and IL-2 induce similar signals, and the cytokine-specificity of IL-2Rα versus IL-15Rα determines cellular responsiveness. These results provide important new insights for specific development of IL-15- versus IL-2-based immunotherapeutics. RNA-Seq is conducted in mouse CD8+ T cells, not treated or treated with IL2 or IL15 for indicated concentrations (1nM or 500nM) and times (4hr or 24hr).

ORGANISM(S): Mus musculus  

SUBMITTER: Dan Feng   Peng Li  Aaron M Ring  Jian-Xin Lin  Vijay Pande  Mathias Rickert  Warren J Leonard  Gregory R Bowman  Engin Özkan  K.Christopher Garcia  Rosanne Spolski  Ignacio Moraga  Suman Mitra 

PROVIDER: E-GEOD-40350 | ArrayExpress | 2012-11-01

SECONDARY ACCESSION(S): GSE40350SRP015113PRJNA173649

REPOSITORIES: GEO, ArrayExpress, ENA

altmetric image

Publications


Interleukin 15 (IL-15) and IL-2 have distinct immunological functions even though both signal through the receptor subunit IL-2Rβ and the common γ-chain (γ(c)). Here we found that in the structure of the IL-15-IL-15Rα-IL-2Rβ-γ(c) quaternary complex, IL-15 binds to IL-2Rβ and γ(c) in a heterodimer nearly indistinguishable from that of the IL-2-IL-2Rα-IL-2Rβ-γ(c) complex, despite their different receptor-binding chemistries. IL-15Rα substantially increased the affinity of IL-15 for IL-2Rβ, and thi  ...[more]

Similar Datasets

2015-06-16 | E-GEOD-64713 | ArrayExpress
2014-02-20 | E-GEOD-41317 | ArrayExpress
2012-04-25 | E-GEOD-36882 | ArrayExpress
| GSE120904 | GEO
2012-09-18 | E-GEOD-39756 | ArrayExpress
2016-08-08 | PXD002386 | Pride
2015-07-07 | E-GEOD-61677 | ArrayExpress
2014-06-25 | E-GEOD-58765 | ArrayExpress
2017-03-31 | MSV000080850 | MassIVE
| GSE76466 | GEO