Molecular mechanisms of lymphocyte-mediated killing.
Lymphocytes kill tumor cells and other target cells by a contact-dependent mechanism. Killer lymphocytes acquire cytoplasmic granules upon lymphokine stimulation and these granules in turn contain potent cytotoxic mediators, some of which have been characterized recently. These include (i) a pore-forming protein (perforin) of 70 kDa that polymerizes into transmembrane tubules in the presence of calcium and that is structurally related to the terminal components (C5b-6, C7, C8 and C9) of the complement cascade, (ii) a cytokine related to tumor necrosis factor and lymphotoxin that causes DNA fragmentation in target cells, and (iii) a family of serine esterases presently without any known function. The relevance of these mediators in lymphocyte-mediated killing is currently being investigated. The identification and characterization of additional putative mediators of cytotoxicity in the future will undoubtedly provide us with a better understanding of the molecular basis of cell-mediated killing.
Young
J D
JD
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021.
Liu
C C
CC
Persechini
P M
PM
D000920:Antibody-Dependent Cell Cytotoxicity; D002463:Cell Membrane Permeability; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000502:physiology; D007694:Killer Cells, Natural / Q000502:physiology*; D008285:Major Histocompatibility Complex; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000502:physiology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
D015938:Complement Membrane Attack Complex; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D003165:Complement System Proteins