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Updated: Aug 9, 2026

Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody (mAb) by Neutralizing TNF Using an In Vitro Bioanalytical Method
16:07

Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody (mAb) by Neutralizing TNF Using an In Vitro Bioanalytical Method

Published on: September 16, 2017

Interactions of tumor necrosis factor (TNF) and TNF receptor family members in the mouse and human

Claudia Bossen1, Karine Ingold, Aubry Tardivel

  • 1Biochemistry Department, University of Lausanne, CH-1066 Epalinges, Switzerland.

The Journal of Biological Chemistry
|March 21, 2006
PubMed

Insights

This study comprehensively maps tumor necrosis factor superfamily (TNFSF) ligand and TNF receptor superfamily (TNFRSF) interactions. It identifies novel interactions, species-specific binding, and uncharacterized receptors, advancing our understanding of immune signaling pathways.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • The tumor necrosis factor superfamily (TNFSF) and TNF receptor superfamily (TNFRSF) are critical regulators of immune responses, inflammation, and cell death.
  • Understanding the precise interactions between these ligands and receptors is essential for deciphering complex biological processes and developing targeted therapies.

Purpose of the Study:

  • To conduct a comprehensive survey of interactions between known TNFSF ligands and TNFRSF members.
  • To identify novel ligand-receptor pairs and characterize species-specific binding patterns between human and mouse systems.
  • To investigate the binding capabilities of previously uncharacterized receptors and the role of ligand oligomerization.

Main Methods:

  • Utilized a flow cytometry-based assay to systematically screen interactions between a panel of TNFSF ligands and TNFRSF members.
  • Employed ligand oligomerization techniques to enhance the detection of weak ligand-receptor interactions.
  • Compared human and mouse ligand-receptor binding profiles to identify cross-reactive, species-specific, and partially species-specific interactions.

Main Results:

  • All tested TNFSF ligands bound one to five TNFRSF receptors, while most receptors interacted with only one to three ligands.
  • Identified several TNFRSF receptors (DR6, RELT, TROY, NGFR, mouse TNFRH3) that did not interact with any known TNFSF ligands.
  • Demonstrated varied species-specificity in ligand-receptor pairs, including cross-reactive, strictly species-specific, and partially species-specific interactions.
  • Observed redundant receptor binding patterns for lymphotoxin alpha and alphabeta in humans but not in mice.
  • Detected weak interactions, such as human TNF with mouse TNFR2, through ligand oligomerization.
  • Characterized two splice variants of mouse APRIL, with one showing weak binding to mouse BAFF-R.

Conclusions:

  • The study provides a detailed map of TNFSF-TNFRSF interactions, revealing a complex network with significant cross-species variations.
  • Several receptors remain uncharacterized regarding their TNFSF ligand interactions, suggesting the existence of unknown ligands or alternative signaling mechanisms.
  • Ligand oligomerization is a crucial method for uncovering weak but biologically relevant interactions.
  • The findings contribute to a deeper understanding of immune regulation and provide a foundation for future research into TNFSF/TNFRSF-mediated diseases.

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