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Interferon gamma signals via a high-affinity multisubunit receptor complex that contains two types of polypeptide

S A Marsters1, D Pennica, E Bach

  • 1Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080, USA.

Proceedings of the National Academy of Sciences of the United States of America
|June 6, 1995
PubMed

Insights

Interferon gamma (IFN-gamma) signaling involves a complex of IFN-gamma with its receptor (IFN-gamma R) alpha and beta chains. This high-affinity complex formation is crucial for initiating IFN-gamma signal transduction.

Area of Science:

  • Immunology
  • Molecular Cell Biology
  • Protein-Protein Interactions

Background:

  • Interferon gamma (IFN-gamma) is a critical cytokine in immune responses.
  • IFN-gamma signaling relies on cell surface receptors, including the IFN-gamma receptor (IFN-gamma R) and an accessory factor.
  • The precise composition and assembly of the IFN-gamma receptor complex remain incompletely understood.

Purpose of the Study:

  • To investigate the complex formation between IFN-gamma and its receptor subunits.
  • To elucidate the stoichiometry and structure of the functional IFN-gamma receptor complex.
  • To determine the role of individual receptor subunits in IFN-gamma binding and signal initiation.

Main Methods:

  • Complex formation studies in solution and at the cell surface.
  • Use of transfected cells expressing different combinations of IFN-gamma receptor subunits (alpha and beta chains).
  • Affinity measurements and functional assays using anti-receptor chain antibodies and soluble receptor domains.

Main Results:

  • IFN-gamma forms a multisubunit complex with IFN-gamma R alpha and beta chains.
  • Observed stoichiometry: ligand, two IFN-gamma R alpha chains, and one or two IFN-gamma R beta chains.
  • High-affinity binding and signaling require both receptor subunits; blocking beta chain function or using soluble domains inhibits IFN-gamma activity.

Conclusions:

  • IFN-gamma signals through a high-affinity, multisubunit receptor complex comprising two distinct receptor chains.
  • The assembly of both IFN-gamma R alpha and beta chains is essential for high-affinity ligand binding and signal transduction.
  • Targeting receptor subunit interactions offers a potential strategy for modulating IFN-gamma activity.

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