Requirement for Ca2+/calmodulin-dependent kinase type IV/Gr in setting the thymocyte selection threshold.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Raman, V; Blaeser, F; Ho, N; Engle, DL; Williams, CB; Chatila, TA

Published Date

  • December 2001

Published In

Volume / Issue

  • 167 / 11

Start / End Page

  • 6270 - 6278

PubMed ID

  • 11714790

Pubmed Central ID

  • 11714790

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.167.11.6270

Language

  • eng