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Human tumour necrosis factors: structure and receptor interactions
B B Aggarwal1, R A Aiyer, D Pennica
1Department of Molecular Immunology and Developmental Biology, Genentech, Inc., South San Francisco, California 94080.
Ciba Foundation Symposium
|January 1, 1987
Summary
Tumor Necrosis Factor-alpha (TNF-alpha) and TNF-beta (lymphotoxin) are cytotoxic factors produced by immune cells. These cytokines share a common receptor and exhibit antiproliferative and antiviral effects.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Immune cell activation yields factors cytotoxic to tumor cells.
- Two such factors, TNF-alpha (myeloid) and TNF-beta (lymphoid), were identified.
Purpose of the Study:
- Investigate the biochemistry, molecular biology, and mechanism of action of TNF-alpha and TNF-beta.
- Characterize their structural properties, genetic linkage, receptor interactions, and biological activities.
Main Methods:
- Purification and sequencing of TNF-alpha and TNF-beta from human cell lines.
- Isolation and characterization of cDNAs using recombinant DNA technology.
- Expression of cDNAs in Escherichia coli for protein production.
Main Results:
- TNF-alpha (157 amino acids, 1 disulfide bond) and TNF-beta (171 amino acids, glycoprotein, no cysteine) were sequenced.
- TNF-alpha and TNF-beta share 31% sequence identity and 52% homology; genes are linked on chromosome 6.
- Both cytokines bind to a common high-affinity receptor, which can be modulated by interferons and lectins, affecting biological responses.
Conclusions:
- TNF-alpha and TNF-beta are distinct yet related cytotoxic cytokines with significant structural and functional similarities.
- Their interaction with a shared receptor and modulation by other factors highlight complex immune regulation.
- Both cytokines possess antiproliferative and direct antiviral activities, underscoring their broad biological relevance.