Distinctions in lymphocyte responses to IL-2 and IL-15 reflect differential ligand binding interactions with the IL-2Rβ chain and suggest differential roles for the IL-2Rα and IL-15Rα subunits

J. L O De Jong, N. L. Farner, Paul M. Sondel

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13 Citations (Scopus)

Abstract

More interleukin 15 (IL-15) than IL-2 was needed to generate comparable proliferative responses by phytohaemagglutinin (PHA) blasts and Tf-1β cells expressing high affinity and intermediate affinity IL-2 receptor (IL-2R) complexes, respectively. The focus of these experiments was to determine the contribution of the shared IL-2 and IL-15 receptor components to these dose-response differences. Some of this difference can be attributed to the role of the IL-2Rβ chain, in that HuMikβ1, a monoclonal antibody recognizing the IL-2Rβ chain, blocks 92.2 ± 2.5% (mean ± SE) of the IL-2 proliferative response by Tf-1β cells but only inhibits 57.9 ± 3.7% of the IL-15 response, indicating that IL-2 and IL-15 may physically utilize the IL-2Rβ chain differently. Monoclonal antibody 341, which recognizes IL-2Rβ but does not inhibit IL-2 binding to the IL-2Rβ chain, blocks 35.4 ± 2.3% of IL-15-stimulated proliferation of PHA blasts, while not affecting the IL-2-stimulated proliferation. Finally, although HuMikβ1 does not inhibit IL-2 responses by PHA blasts bearing high affinity IL-2 receptors, HuMikβ1 does block IL-15-stimulated proliferation by these same cells bearing high affinity IL-15 receptors (88.5 ± 1.6% inhibition). This indicates that the role of IL-15Rα in the high affinity IL-15R complex is distinct from that of IL-2Rα in the high affinity IL-2R complex. Overall, these studies show that the physical interactions of the IL-2Rβγ(c) complex with IL-2 are different than the interactions with IL-15.

Original languageEnglish (US)
Pages (from-to)920-930
Number of pages11
JournalCytokine
Volume10
Issue number12
DOIs
StatePublished - Dec 1998

Fingerprint

Interleukin-15
Lymphocytes
Interleukin-2 Receptors
Interleukin-2
Ligands
Interleukin-15 Receptors
Phytohemagglutinins
Bearings (structural)
Monoclonal Antibodies
Cells
Cell Proliferation

Keywords

  • Cytokine receptors
  • Interleukin 15
  • Interleukin 2
  • Lymphocytes

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Immunology
  • Immunology and Allergy

Cite this

@article{ca472d5ba7a84c13a7839184fcaf3221,
title = "Distinctions in lymphocyte responses to IL-2 and IL-15 reflect differential ligand binding interactions with the IL-2Rβ chain and suggest differential roles for the IL-2Rα and IL-15Rα subunits",
abstract = "More interleukin 15 (IL-15) than IL-2 was needed to generate comparable proliferative responses by phytohaemagglutinin (PHA) blasts and Tf-1β cells expressing high affinity and intermediate affinity IL-2 receptor (IL-2R) complexes, respectively. The focus of these experiments was to determine the contribution of the shared IL-2 and IL-15 receptor components to these dose-response differences. Some of this difference can be attributed to the role of the IL-2Rβ chain, in that HuMikβ1, a monoclonal antibody recognizing the IL-2Rβ chain, blocks 92.2 ± 2.5{\%} (mean ± SE) of the IL-2 proliferative response by Tf-1β cells but only inhibits 57.9 ± 3.7{\%} of the IL-15 response, indicating that IL-2 and IL-15 may physically utilize the IL-2Rβ chain differently. Monoclonal antibody 341, which recognizes IL-2Rβ but does not inhibit IL-2 binding to the IL-2Rβ chain, blocks 35.4 ± 2.3{\%} of IL-15-stimulated proliferation of PHA blasts, while not affecting the IL-2-stimulated proliferation. Finally, although HuMikβ1 does not inhibit IL-2 responses by PHA blasts bearing high affinity IL-2 receptors, HuMikβ1 does block IL-15-stimulated proliferation by these same cells bearing high affinity IL-15 receptors (88.5 ± 1.6{\%} inhibition). This indicates that the role of IL-15Rα in the high affinity IL-15R complex is distinct from that of IL-2Rα in the high affinity IL-2R complex. Overall, these studies show that the physical interactions of the IL-2Rβγ(c) complex with IL-2 are different than the interactions with IL-15.",
keywords = "Cytokine receptors, Interleukin 15, Interleukin 2, Lymphocytes",
author = "{De Jong}, {J. L O} and Farner, {N. L.} and Sondel, {Paul M.}",
year = "1998",
month = "12",
doi = "10.1006/cyto.1998.0377",
language = "English (US)",
volume = "10",
pages = "920--930",
journal = "Cytokine",
issn = "1043-4666",
publisher = "Academic Press Inc.",
number = "12",

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T1 - Distinctions in lymphocyte responses to IL-2 and IL-15 reflect differential ligand binding interactions with the IL-2Rβ chain and suggest differential roles for the IL-2Rα and IL-15Rα subunits

AU - De Jong, J. L O

AU - Farner, N. L.

AU - Sondel, Paul M.

PY - 1998/12

Y1 - 1998/12

N2 - More interleukin 15 (IL-15) than IL-2 was needed to generate comparable proliferative responses by phytohaemagglutinin (PHA) blasts and Tf-1β cells expressing high affinity and intermediate affinity IL-2 receptor (IL-2R) complexes, respectively. The focus of these experiments was to determine the contribution of the shared IL-2 and IL-15 receptor components to these dose-response differences. Some of this difference can be attributed to the role of the IL-2Rβ chain, in that HuMikβ1, a monoclonal antibody recognizing the IL-2Rβ chain, blocks 92.2 ± 2.5% (mean ± SE) of the IL-2 proliferative response by Tf-1β cells but only inhibits 57.9 ± 3.7% of the IL-15 response, indicating that IL-2 and IL-15 may physically utilize the IL-2Rβ chain differently. Monoclonal antibody 341, which recognizes IL-2Rβ but does not inhibit IL-2 binding to the IL-2Rβ chain, blocks 35.4 ± 2.3% of IL-15-stimulated proliferation of PHA blasts, while not affecting the IL-2-stimulated proliferation. Finally, although HuMikβ1 does not inhibit IL-2 responses by PHA blasts bearing high affinity IL-2 receptors, HuMikβ1 does block IL-15-stimulated proliferation by these same cells bearing high affinity IL-15 receptors (88.5 ± 1.6% inhibition). This indicates that the role of IL-15Rα in the high affinity IL-15R complex is distinct from that of IL-2Rα in the high affinity IL-2R complex. Overall, these studies show that the physical interactions of the IL-2Rβγ(c) complex with IL-2 are different than the interactions with IL-15.

AB - More interleukin 15 (IL-15) than IL-2 was needed to generate comparable proliferative responses by phytohaemagglutinin (PHA) blasts and Tf-1β cells expressing high affinity and intermediate affinity IL-2 receptor (IL-2R) complexes, respectively. The focus of these experiments was to determine the contribution of the shared IL-2 and IL-15 receptor components to these dose-response differences. Some of this difference can be attributed to the role of the IL-2Rβ chain, in that HuMikβ1, a monoclonal antibody recognizing the IL-2Rβ chain, blocks 92.2 ± 2.5% (mean ± SE) of the IL-2 proliferative response by Tf-1β cells but only inhibits 57.9 ± 3.7% of the IL-15 response, indicating that IL-2 and IL-15 may physically utilize the IL-2Rβ chain differently. Monoclonal antibody 341, which recognizes IL-2Rβ but does not inhibit IL-2 binding to the IL-2Rβ chain, blocks 35.4 ± 2.3% of IL-15-stimulated proliferation of PHA blasts, while not affecting the IL-2-stimulated proliferation. Finally, although HuMikβ1 does not inhibit IL-2 responses by PHA blasts bearing high affinity IL-2 receptors, HuMikβ1 does block IL-15-stimulated proliferation by these same cells bearing high affinity IL-15 receptors (88.5 ± 1.6% inhibition). This indicates that the role of IL-15Rα in the high affinity IL-15R complex is distinct from that of IL-2Rα in the high affinity IL-2R complex. Overall, these studies show that the physical interactions of the IL-2Rβγ(c) complex with IL-2 are different than the interactions with IL-15.

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KW - Interleukin 2

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