Editors' ChoiceImmunology

Granzyme B Receptor

Science's STKE  07 Nov 2000:
Vol. 2000, Issue 57, pp. tw8
DOI: 10.1126/stke.2000.57.tw8

One key component of the mechanism by which cytotoxic T lymphocytes (CTLs) attack virus-infected or tumor cells is release of cytolytic molecules like the protease granzyme B (grB). Motyka et al. report the discovery that grB uptake is mediated by a receptor--the cation-independent mannose 6-phosphate receptor (CI-MPR), also known as the insulin-like growth factor II receptor. Mouse fibroblast L cells lacking CI-MPR were resistant to apoptosis caused by grB. In a transplant rejection model in mice, donor cells that expressed CI-MPR were rejected, whereas cells lacking the receptor remained and expanded. The CI-MPR provides a potential target for therapeutic modulation of CTL-induced killing.

Motyka, B., Korbutt, G., Pinkoski, M.J., Heibein, J.A., Caputo, A., Hobman, M., Garry, M., Shostak, I., Sawchuk, T., Holmes, C.F.B., Gauldie, J., and Bleackley, R.C. (2000) Mannose 6-phosphate/insulin-like growth factor II receptor is a death receptor for granzyme B during cytotoxic T cell-induced apoptosis. Cell 103:491-500. [Online Journal]