Author/Authors :
Bruce Motyka، نويسنده , , Gregory Korbutt، نويسنده , , Michael J. Pinkoski، نويسنده , , Jeffrey A Heibein، نويسنده , , Antonio Caputo، نويسنده , , Marita Hobman، نويسنده , , Michele Barry، نويسنده , , Irene Shostak، نويسنده , , Tracy Sawchuk، نويسنده , , Charles F.B Holmes، نويسنده , , Jack Gauldie، نويسنده , , R.Chris Bleackley، نويسنده ,
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.
