Abstract
Clonal selection of T lymphocytes is essential for establishing self/non-self discrimination of immune recognition. It is known that cell surface signals such as avidity and valency of TCR-ligand interactions influence the fate of individual thymocytes, founding a primary repertoire of T cells. However, intracellular signals that govern positive and negative selection in the thymus have been unclear. The present study using the retroviral gene transfer technique shows that MKK1 activation in developing T cells is sufficient for providing positive selection signals. We also show that the MKK6-p38 signaling pathway is critically involved in inducing negative selection of thymocytes. These results suggest that intracellular signals through different MAP kinase cascades selectively guide positive and negative selection of T lymphocytes.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Base Sequence
-
Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
-
Calcium-Calmodulin-Dependent Protein Kinases / genetics
-
Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
-
Cell Differentiation
-
DNA Primers / genetics
-
Enzyme Activation
-
Enzyme Inhibitors / pharmacology
-
Female
-
Flavonoids / pharmacology
-
Gene Transfer Techniques
-
Humans
-
Imidazoles / pharmacology
-
MAP Kinase Kinase 1
-
Male
-
Mice
-
Mice, Inbred BALB C
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Mice, Transgenic
-
Mitogen-Activated Protein Kinase Kinases*
-
Mitogen-Activated Protein Kinases*
-
Protein Serine-Threonine Kinases / antagonists & inhibitors
-
Protein Serine-Threonine Kinases / genetics
-
Protein Serine-Threonine Kinases / metabolism*
-
Protein-Tyrosine Kinases / antagonists & inhibitors
-
Protein-Tyrosine Kinases / genetics
-
Protein-Tyrosine Kinases / metabolism*
-
Pyridines / pharmacology
-
Retroviridae / genetics
-
Signal Transduction
-
T-Lymphocytes / cytology
-
T-Lymphocytes / enzymology*
-
T-Lymphocytes / immunology*
-
p38 Mitogen-Activated Protein Kinases
Substances
-
DNA Primers
-
Enzyme Inhibitors
-
Flavonoids
-
Imidazoles
-
Pyridines
-
Protein-Tyrosine Kinases
-
Protein Serine-Threonine Kinases
-
Calcium-Calmodulin-Dependent Protein Kinases
-
Mitogen-Activated Protein Kinases
-
p38 Mitogen-Activated Protein Kinases
-
MAP Kinase Kinase 1
-
MAP2K1 protein, human
-
Map2k1 protein, mouse
-
Mitogen-Activated Protein Kinase Kinases
-
SB 203580
-
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one