First Author | Raman V | Year | 2001 |
Journal | J Immunol | Volume | 167 |
Issue | 11 | Pages | 6270-8 |
PubMed ID | 11714790 | Mgi Jnum | J:72830 |
Mgi Id | MGI:2153664 | Doi | 10.4049/jimmunol.167.11.6270 |
Citation | Raman V, et al. (2001) Requirement for Ca(2+)/Calmodulin-Dependent Kinase Type IV/Gr in Setting the Thymocyte Selection Threshold. J Immunol 167(11):6270-8 |
abstractText | The outcome of thymocyte selection is influenced by the nature of Ca(2+) signals transduced by the TCR. Robust Ca(2+) 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 Ca(2+) signals, we examined selection events in mice lacking Ca(2+)/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr), which is enriched in thymocytes. CaMKIV/Gr-deficient thymocytes exhibited impaired positive selection and defective Ca(2+)-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. |