Tyrosine kinase triggering in thymocytes undergoing positive selection.
Developing T cells undergo distinct selection processes that determine the T cell receptor (TcR) repertoire. One of these processes is positive selection. Positive selection involves the differentiation to mature T cells of thymocytes bearing TcR capable of recognizing antigens in the context of self-major histocompatibility complex (MHC) molecules. To study the potential involvement of tyrosine phosphorylation in the mechanism of positive selection, we have analyzed the activities of the tyrosine kinases pp56lck and pp59fyn in thymocytes expressing a unique TcR specific for HY antigen+ H-2 Db. Thymocytes undergoing positive selection displayed higher kinase specific activities of pp56lck and pp59fyn than nonselecting thymocytes. Furthermore, these increases in kinase activities were found only in the CD4+CD8+ subpopulation of thymocytes, where the selection process is believed to occur. These data suggest that tyrosine phosphorylation is part of the intracellular signals involved in MHC class I-driven positive selection from CD4+CD8+ immature thymocytes to CD4-CD8+ mature cells.
Carrera
A C
AC
Department of Pathology, Dana-Farber Cancer Institute, Boston, MA 02115.
Baker
C
C
Roberts
T M
TM
Pardoll
D M
DM
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002454:Cell Differentiation; D004789:Enzyme Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D051076:Proto-Oncogene Proteins c-fyn; D013601:T-Lymphocytes / Q000201:enzymology* / Q000502:physiology
D015704:CD4 Antigens; D016827:CD8 Antigens; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn