Interaction of IL-15 with the shared IL-2 receptor β and γc subunits: The IL-15/β/γc receptor-ligand complex is less stable than the IL-2/β/γc receptor-ligand complex

Jill L O De Jong, Nancy L. Farner, Michael B. Widmer, Judith G. Giri, Paul M. Sondel

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

This study was designed to compare the interactions of IL-2 and IL-15 with the IL-2Rβ and IL-2Rγc subunits, as differences in receptor interactions between IL-2 and IL-15 might contribute to the functional differences between these two cytokines. The results suggest the existence of a human IL-15Rα subunit, although physical evidence of this molecule was not obtained. Proliferation of anti-CD3 (OKT3)-stimulated human PBL was compared for responsiveness to IL-2, IL-15, and F42K, an IL-2 mutant that does not bind the IL-2Rα chain. F42K was more potent than IL-15 in activating a dose-dependent response. This fact, along with Scatchard binding analyses of IL-15 on OKT3 blasts and YT cells revealing both high and intermediate affinity receptors, supports the existence of IL-15Rα on these cells. Additional characterization of the IL-15R utilized covalent cross-linking to affinity label IL-2R and IL-15R on YT cells and OKT3 blasts. Consistent with previously reported functional data, IL-2Rα was not co-precipitated from the [125I]IL-15 receptor-ligand complex, demonstrating that IL-15 does not interact physically with the IL-2Rα subunit. While IL-2Rα did co-precipitate with IL-2Rβ and IL-2Rγc in the presence of IL-2, IL-15Rα did not co-precipitate with the IL-2Rβ/γc complex. Finally, YT cells equilibrated with IL-2 and then precipitated through IL-2Rβ showed that IL-2Rβ and IL-2Rγc co-precipitate in a 1:1 ratio, while only IL-2Rβ was found in the immunoprecipitates of YT cells equilibrated with IL-15. This indicates that IL-15 creates a less stable bridge between the IL-2Rβ and IL-2Rγc chains than does IL-2 on YT cells. This result was identical for both surface-iodinated YT cells and immunoprecipitates that were probed for IL-2Rβ and IL-2Rγc on Western blots.

Original languageEnglish (US)
Pages (from-to)1339-1348
Number of pages10
JournalJournal of Immunology
Volume156
Issue number4
StatePublished - Feb 15 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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