Stimulation of NK-like YT cells via leukocyte function-associated antigen (LFA)-1. Possible involvement of LFA-1-associated tyrosine kinase in signal transduction after recognition of NK target cells.
The YTA-1 anti-LFA-1 alpha mAb activates protein tyrosine kinase (PTK), augments NK cytotoxicity, and induces proliferation of fresh CD3- large granular lymphocytes. We demonstrate here that LFA-1 is physically associated in the YT human NK-like cell line cells with a PTK(s) that is distinct from Src family PTKs such as Lck, Fyn, or Lyn. In vitro kinase assays revealed similar association of protein kinase activity with LFA-1 in normal CD3- large granular lymphocytes. Tyrosine phosphorylation of the proteins associated with LFA-1 drastically increased in YT cells after stimulation with NK-sensitive K562 cells but not with NK-resistant P815 cells. Furthermore, pretreatment of YT cells with TS1/22 anti-LFA-1 alpha and TS1/18 anti-LFA-1 beta mAbs abrogated not only the cytotoxicity against K562 cells but also an increase in tyrosine phosphorylation of LFA-1-associated molecules induced by K562 stimulation. These results provide biochemical evidence that the PTK(s) associated with LFA-1 is involved in the signal transduction that follows the recognition of NK target cells.
Department of Late Effect Studies, Kyoto University, Japan.
K
K
Sugie
Y
Y
Minami
T
T
Kawakami
A
A
Uchida
D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004789:Enzyme Activation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D011505:Protein-Tyrosine Kinases