Requirement for Ca2+/calmodulin-dependent kinase type IV/Gr in setting the thymocyte selection threshold.
The outcome of thymocyte selection is influenced by the nature of Ca2+ signals transduced by the TCR. Robust Ca2+ responses characterize high-affinity, negatively selecting peptide/TCR interactions, while modest responses typify lower-affinity, positively selecting interactions. To elucidate mechanisms by which thymocytes decode distinct Ca2+ signals, we examined selection events in mice lacking Ca2+/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr), which is enriched in thymocytes. CaMKIV/Gr-deficient thymocytes exhibited impaired positive selection and defective Ca2+-dependent gene transcription. Significantly, CaMKIV/Gr deficiency raised the selection threshold of peptide/TCR interactions such that a peptide that normally induced weak negative selection instead promoted positive selection. These results demonstrate an important role for CaMKIV/Gr in sensitizing thymocytes to selection by low-affinity peptides.
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Related Subject Headings
- Thymus Gland
- T-Lymphocytes
- Receptors, Antigen, T-Cell
- Mice, Transgenic
- Mice, Knockout
- Mice, Inbred C57BL
- Mice, Inbred AKR
- Mice
- Immunology
- Hemoglobins
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Thymus Gland
- T-Lymphocytes
- Receptors, Antigen, T-Cell
- Mice, Transgenic
- Mice, Knockout
- Mice, Inbred C57BL
- Mice, Inbred AKR
- Mice
- Immunology
- Hemoglobins