Lck-independent triggering of T-cell antigen receptor signal transduction by staphylococcal enterotoxins.
Superantigens (SAgs) activate T-cells in a manner specific to the Vbeta region of the T-cell antigen receptor. Stimulations by SAgs provoke drastic T-cell activation that leads to programmed cell death or the anergic state of responding cells. To characterize the signal transduction pathway initiated by SAgs, mutant lines derived from the human leukemic T-cell line Jurkat were tested for their reactivities against prototypic SAgs, staphylococcal enterotoxins. The J.CaM1.6 cell line, which lacks Lck expression and lost reactivity against T-cell antigen receptor-mediated stimulation, was activated by staphylococcal enterotoxins in a manner indistinguishable from the Jurkat cell line. In contrast, the J.45. 01 cell line, which lacks expression of functional CD45, showed severely impaired reactivity. The role of Lck appears to be replaced by another Src family protein-tyrosine kinase, Fyn. In J.CaM1.6 cells, Fyn was rapidly phosphorylated and activated after staphylococcal enterotoxin treatment. The kinase-inactive mutant of Fyn significantly suppressed the reactivity against staphylococcal enterotoxin E in J.CaM1.6 cells, and the expression of the active form of Fyn reconstituted reactivity against staphylococcal enterotoxin E in J.45.01 cells. These results demonstrate that SAgs activate T-cells in an Lck-independent pathway and that Fyn plays a critical role in the process.
Yamasaki
S
S
Division of Cell and Information, Precursor Research for Embryonic Science and Technology, Japan Science and Technology Corporation, Tokyo 194, Japan.
Tachibana
M
M
Shinohara
N
N
Iwashima
M
M
D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D002118:Calcium / Q000494:pharmacology; D002999:Clone Cells; D004768:Enterotoxins / Q000494:pharmacology*; D017930:Genes, Reporter; D006801:Humans; D019169:Jurkat Cells; D037181:Lectins, C-Type; D008156:Luciferases / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D016296:Mutagenesis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D013210:Staphylococcus; D013211:Staphylococcus aureus; D018089:Superantigens / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002118:Calcium; D004768:Enterotoxins; D037181:Lectins, C-Type; D008156:Luciferases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D011518:Proto-Oncogene Proteins; D051076:Proto-Oncogene Proteins c-fyn; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; D019061:src-Family Kinases; D000099192:CD69 Antigens; C049463:enterotoxin E, Staphylococcal; C494957:FYN protein, human