Molecular mechanisms of lymphocyte-mediated cytotoxicity.
Granule-mediated cytotoxicity is the major mechanism for lymphocytes to kill viruses, intracellular bacteria and tumors. The cytotoxic granules move to the immunological synapse by exocytosis after recognition of a killer cell. The contents of the granules are delivered into target cells with the help of perforin by endocytosis. A group of serine protease granzymes cleave their critical substrates to initiate DNA damage and cell death. The most abundant granzymes are granzyme A and B. They induce cell death through alternate and nonoverlapping pathways. The substrates and functions of the majority of the orphan granzymes have not yet been identified. It is possible that the diversity of granzymes provides fail-safe mechanisms for killing viruses and tumor cells.
Fan
Zusen
Z
National Laboratory of Biomacromolecules, Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. zusenfan2001@yahoo.com
Zhang
Qixiang
Q
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D017209:Apoptosis; D003602:Cytotoxicity, Immunologic; D053804:Granzymes / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular; D054353:Perforin / Q000378:metabolism*; D022142:Secretory Vesicles; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; C075005:GNLY protein, human; D054353:Perforin; D053804:Granzymes