Differential expression of protein tyrosine kinases and their phosphorylation in murine Th1 cells anergized with class II MHC-peptide complexes.
In resting T cell clones, antigen presentation with immobilized anti-CD3 or anti-T cell receptor (TCR) is known to result in a state of anergy as characterized by unresponsiveness to normal antigenic restimulation. Similarly, T cell unresponsiveness could be induced by immobilized (plate-coated) complexes of purified class II MHC and antigenic peptide. It is not clearly defined whether the engagement of TCR by immobilized anti-TCR or immobilized class II MHC-peptide complexes generates similar or differential signals during the induction of T cell unresponsiveness. In order to address the initial signalling events induced by TCR occupancy with anti-TCR and class II MHC-peptide molecules, the expression of three critical protein tyrosine kinases (PTK) and their phosphorylation were investigated in the present study using a murine T cell clone (HS17) restricted for IAS and myelin basic protein (MBP (91-103)) peptide. The anergic T cells induced by immobilized IAS-MBP (91-103) complex or anti-TCR (H57) showed differential expression of lck (56 kDa) and Zap-70 (70 kDa) proteins. In both systems, however, the induction of T cell unresponsiveness was accompanied by increased level of fyn (59 kDa) expression. When analysed for the total tyrosine phosphorylation of PTK, anergic HS17 T cells induced by both molecules showed increased phosphorylation associated with only the fyn protein. These results suggest that the signal transduction events induced by immobilized class II MHC-peptide complexes and anti-TCR are distinct, although both can initiate signals that lead to increased fyn expression and phosphorylation. In addition, the present study supports the evidence for the important functional association of fyn protein with direct TCR engagement in T cell signalling.
Yu
S C
SC
Anergen Inc., Redwood City, California, USA.
Nag
B
B
D000818:Animals; D017635:Clonal Anergy; D002999:Clone Cells; D000949:Histocompatibility Antigens Class II / Q000008:administration & dosage; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D018417:Th1 Cells / Q000201:enzymology* / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase
D000949:Histocompatibility Antigens Class II; D010455:Peptides; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse