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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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Mannose 6-phosphate/insulin-like growth factor II receptor is a death receptor for granzyme B during cytotoxic T

B Motyka1, G Korbutt, M J Pinkoski

  • 1Department of Biochemistry, University of Alberta, Edmonton, Canada.

Cell
|November 18, 2000
PubMed

Insights

Cytotoxic T cells use granzyme B to induce target cell apoptosis. Researchers identified the cation-independent mannose 6-phosphate/insulin-like growth factor receptor (CI-MPR) as the key cell surface receptor for granzyme B entry.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Medicine

Background:

  • Granzyme B is essential for cytotoxic T cell-mediated apoptosis.
  • Perforin-independent entry of granzyme B into target cells suggests a cell surface receptor.
  • Identifying this receptor is crucial for understanding immune responses and developing therapies.

Purpose of the Study:

  • To identify the cell surface receptor responsible for granzyme B entry into target cells.
  • To investigate the role of this receptor in cytotoxic T cell-mediated apoptosis and immune rejection.
  • To explore the potential of targeting this interaction for immunotherapy and understanding immune evasion.

Main Methods:

  • Utilized biochemical assays to investigate the interaction between granzyme B and potential cell surface receptors.
  • Employed functional assays to assess the impact of inhibiting the granzyme B-receptor interaction on granzyme B binding, uptake, and apoptosis induction.
  • Evaluated the necessity of the identified receptor for cytotoxic T cell-mediated apoptosis in vitro and allogeneic cell rejection in vivo.

Main Results:

  • Identified the cation-independent mannose 6-phosphate/insulin-like growth factor receptor (CI-MPR) as the cell surface receptor for granzyme B.
  • Demonstrated that inhibiting the granzyme B-CI-MPR interaction blocked granzyme B binding, cellular uptake, and subsequent apoptosis.
  • Confirmed that CI-MPR expression is critical for cytotoxic T cell-induced apoptosis and allogeneic cell rejection.

Conclusions:

  • The cation-independent mannose 6-phosphate/insulin-like growth factor receptor (CI-MPR) mediates granzyme B entry into target cells.
  • This interaction is vital for cytotoxic T cell function in apoptosis induction and immune surveillance.
  • The granzyme B-CI-MPR pathway represents a novel therapeutic target for immunotherapy and a potential mechanism for tumor immune evasion.

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