Mannose 6-Phosphate/Insulin-like Growth Factor II Receptor Is a Death Receptor for Granzyme B during Cytotoxic T Cell–Induced Apoptosis Academic Article uri icon

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abstract

  • The serine proteinase granzyme B is crucial for the rapid induction of target cell apoptosis by cytotoxic T cells. Granzyme B was recently demonstrated to enter cells in a perforin-independent manner, thus predicting the existence of a cell surface receptor(s). We now present evidence that this receptor is the cation-independent mannose 6-phosphate/insulin-like growth factor receptor (CI-MPR). Inhibition of the granzyme B-CI-MPR interaction prevented granzyme B cell surface binding, uptake, and the induction of apoptosis. Significantly, expression of the CI-MPR was essential for cytotoxic T cell-mediated apoptosis of target cells in vitro and for the rejection of allogeneic cells in vivo. These results suggest a novel target for immunotherapy and a potential mechanism used by tumors for immune evasion.

authors

  • Motyka, Bruce
  • Korbutt, Gregory
  • Pinkoski, Michael J
  • Heibein, Jeffrey A
  • Caputo, Antonio
  • Hobman, Marita
  • Barry, Michele
  • Shostak, Irene
  • Sawchuk, Tracy
  • Holmes, Charles FB
  • Gauldie, Jack
  • Bleackley, R Chris

publication date

  • October 2000

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