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Requirement for Ca2+/calmodulin-dependent kinase type IV/Gr in setting the thymocyte selection threshold. J Immunol 2001 Dec 01;167(11):6270-8

Date

11/21/2001

Pubmed ID

11714790

DOI

10.4049/jimmunol.167.11.6270

Scopus ID

2-s2.0-0035529003   22 Citations

Abstract

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.

Author List

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

Author

Calvin B. Williams MD, PhD Chief, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Breeding
Calcium
Calcium-Calmodulin-Dependent Protein Kinase Type 4
Calcium-Calmodulin-Dependent Protein Kinases
Cell Differentiation
Crosses, Genetic
Gene Expression Regulation, Developmental
H-Y Antigen
Hemoglobins
Mice
Mice, Inbred AKR
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Receptors, Antigen, T-Cell
T-Lymphocytes
Thymus Gland