Requirement for Ca2+/calmodulin-dependent kinase type IV/Gr in setting the thymocyte selection threshold.
J Immunol
; 167(11): 6270-8, 2001 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-11714790
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Timo
/
Linfocitos T
/
Proteínas Quinasas Dependientes de Calcio-Calmodulina
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos