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Perforin and its role in T lymphocyte-mediated cytolysis

B Lowin1, O Krähenbühl, C Müller

  • 1Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.

Experientia
|October 15, 1992
PubMed

Insights

Cytotoxic T lymphocytes (CTL) kill tumor and virus-infected cells by releasing granule proteins. Researchers discovered perforin, a key protein forming pores in target cell membranes, crucial for immune defense.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Cytotoxic T lymphocytes (CTL) are vital for immune defense against tumors and viral infections.
  • CTL-mediated killing involves the release of granule-stored molecules upon effector-target cell contact.
  • Pore-like lesions observed on target cell membranes during CTL attack resemble complement attack structures.

Purpose of the Study:

  • To elucidate the lytic mechanism employed by cytotoxic T lymphocytes (CTL).
  • To identify and characterize the molecules responsible for CTL-mediated cytotoxicity.
  • To investigate the role of perforin in the cytotoxic process.

Main Methods:

  • Isolation of CTL granules using nitrogen cavitation and Percoll gradient centrifugation.
  • Purification of proteins from CTL granules.
  • Electron microscopy to visualize membrane lesions.
  • Gene ablation in mice to study perforin function.

Main Results:

  • CTL granules retain cytotoxic activity.
  • A membranolytic protein, perforin, was discovered, capable of polymerizing into pore-like structures.
  • Serine esterases, lysosomal enzymes, and proteoglycans were also identified in CTL granules.
  • Pore-like structures formed by perforin resemble those seen in complement-mediated lysis.

Conclusions:

  • Perforin is a key component of the CTL lytic mechanism, forming pores in target cell membranes.
  • The study provides insights into the molecular basis of CTL-mediated cytotoxicity.
  • Further research involving gene ablation in mice is ongoing to fully define perforin's role.

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