NKG2D-mediated activation of cytotoxic lymphocytes: unique signaling pathways and distinct functional outcomes.
NKG2D is an important immunosurveillance receptor that triggers a unique signal transduction pathway resulting in a variety of functional outcomes. NKG2D couples to the non-ITAM-containing DAP10 and initiates at least two signaling branches that are both required for cytotoxicity. Transformed, infected, or healthy cells can express NKG2D ligands, and NKG2D(+) lymphocytes can be unaffected, costimulated, or fully activated by the NKG2D-ligand interaction. The NKG2D-mediated response can be modulated by factors such as cytokine milieu and possibly the particular ligand expressed. Thus, this nontraditional NKG2D-DAP10 initiated signal pathway enables lymphocytes to differentially respond to ligands based on the cellular environment.
Upshaw
Jadee L
JL
Department of Immunology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. upshaw.jadee@mayo.edu
Leibson
Paul J
PJ
D000818:Animals; D006801:Humans; D008213:Lymphocyte Activation; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000276:immunology*; D055607:Receptors, Natural Killer Cell; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell