The human interferon alpha/beta receptor: characterization and molecular cloning

Area of Science:

• Immunology
• Molecular Biology
• Cellular Biology

Background:

• Type I interferons (IFNs), including IFN-alpha and IFN-beta, are critical cytokines involved in antiviral and antitumor responses.
• Understanding the receptor mediating these responses is essential for developing therapeutic strategies.

Purpose of the Study:

• To identify and characterize the universal ligand-binding receptor for human type I IFNs.
• To elucidate the structure and function of the IFN-alpha/beta receptor.

Main Methods:

• Purification and sequencing of a soluble 40 kDa IFN-alpha/beta receptor (p40) from urine.
• Antibody generation against p40 for functional blocking and immunoprecipitation assays.
• Isolation and expression of a cDNA encoding the IFN-alpha/beta receptor.
• Analysis of receptor subunit structure and association with intracellular signaling molecules.

Main Results:

• A soluble 40 kDa receptor (p40) that blocks type I IFN activity was identified.
• Antibodies against p40 inhibited type I IFN activity and precipitated the cellular 102 kDa receptor.
• The cellular receptor is a disulfide-linked dimer of 51 kDa subunits.
• A cDNA encoding a 331 amino acid receptor was isolated, with the ectodomain matching p40.
• The receptor physically associates with the tyrosine kinase JAK1, indicating a role in signal transduction.

Conclusions:

• A universal receptor for human IFN-alpha and IFN-beta has been identified and characterized.
• This receptor is a disulfide-linked dimer involved in both ligand binding and signal transduction via JAK1 association.
• The findings provide a molecular basis for understanding type I IFN action and potential therapeutic interventions.