Related Experiment Videos
T-cell activation molecule 4-1BB binds to extracellular matrix proteins
N J Chalupny1, R Peach, D Hollenbaugh
1Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
Summary
The 4-1BB protein binds to extracellular matrix proteins like fibronectin, suggesting a role in cell adhesion. Carbohydrates appear to mediate this interaction, offering new insights into T-cell function.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- 4-1BB is a cell surface protein found on activated T cells.
- Its function remains largely unknown, despite homology to the nerve growth factor receptor superfamily.
Purpose of the Study:
- To investigate the function of 4-1BB.
- To identify ligands for 4-1BB, particularly extracellular matrix (ECM) components.
- To explore the role of carbohydrates in 4-1BB-ECM interactions.
Main Methods:
- Preparation of a 4-1BB-immunoglobulin fusion protein (4-1BB Rg) for binding studies.
- Immunohistochemical analysis to detect 4-1BB ligand expression.
- Expression of 4-1BB in COS cells to test binding to various ECM proteins.
- Inhibition assays using carbohydrate polymers (fucoidan, dextran sulfate, heparin sulfate) to elucidate binding mechanisms.
Main Results:
- 4-1BB Rg bound to numerous tissues, indicating widespread ligand expression.
- 4-1BB directly bound fibronectin, vitronectin, laminin, and collagen VI, but not collagen I.
- Binding was independent of RGD and CS-1 sequences but involved multiple fibronectin regions.
- Fucoidan completely blocked 4-1BB-ECM binding, while dextran sulfate and heparin sulfate partially blocked it.
Conclusions:
- 4-1BB interacts with multiple extracellular matrix proteins.
- Carbohydrate moieties, particularly sulfated polysaccharides, play a significant role in mediating 4-1BB-ECM adhesion.
- These findings suggest a novel mechanism for T-cell adhesion and interaction with the extracellular environment.