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To: nigel bates who wrote (413)	11/1/2000 5:20:17 PM
From: tnsaf	Respond to of 7143

There was a front page article on one of Canada's national newspapers about this Cell article. The newspaper article had some factual errors, but there was a reference to the original along with comments by one of the authors and others. Jason Cell, Vol. 103, 491–500, October, 2000, Copyright © 2000 by Mannose 6-Phosphate/Insulin-like Growth Factor II Receptor Is a Death Receptor for Granzyme B during Cytotoxic T Cell–Induced Apoptosis Bruce Motyka1, Gregory Korbutt2, Michael J. Pinkoski1, Jeffrey A. Heibein1, Antonio Caputo1, Marita Hobman1, Michele Barry1, Irene Shostak1, Tracy Sawchuk1, Charles F. B. Holmes1, Jack Gauldie3, and R. Chris Bleackley1 1 Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada 2 Department of Surgery, University of Alberta, Edmonton, Alberta T6G 2H7, Canada 3 Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada Corresponding author: R. Chris Bleackley§, 780 492 3968 (phone), 780 492 0886 (fax), chris.bleackley@ualberta.ca 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.