A critical lineage-nonspecific role for pTalpha in mediating allelic and isotypic exclusion in TCRbeta-transgenic mice.

Détails

ID Serval
serval:BIB_520E6AC85561
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A critical lineage-nonspecific role for pTalpha in mediating allelic and isotypic exclusion in TCRbeta-transgenic mice.
Périodique
European journal of immunology
Auteur⸱e⸱s
Ferrero I., Grosjean F., Fiorini E., MacDonald H.R.
ISSN
0014-2980
Statut éditorial
Publié
Date de publication
2007
Peer-reviewed
Oui
Volume
37
Numéro
11
Pages
3220-3228
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Although it is well established that early expression of TCRbeta transgenes in the thymus leads to efficient inhibition of both endogenous TCRbeta and TCRgamma rearrangement (also known as allelic and "isotypic" exclusion, respectively) the role of pTalpha in these processes remains controversial. Here, we have systematically re-evaluated this issue using three independent strains of TCRbeta-transgenic mice that differ widely in transgene expression levels, and a sensitive intracellular staining assay that detects endogenous TCRVbeta expression in individual immature thymocytes. In the absence of pTalpha, both allelic and isotypic exclusion were reversed in all three TCRbeta-transgenic strains, clearly demonstrating a general requirement for pre-TCR signaling in the inhibition of endogenous TCRbeta and TCRgamma rearrangement. Both allelic and isotypic exclusion were pTalpha dose dependent when transgenic TCRbeta levels were subphysiological. Moreover, pTalpha-dependent allelic and isotypic exclusion occurred in both alphabeta and gammadelta T cell lineages, indicating that pre-TCR signaling can potentially be functional in gammadelta precursors. Finally, levels of endogenous RAG1 and RAG2 were not down-regulated in TCRbeta-transgenic immature thymocytes undergoing allelic or isotypic exclusion. Collectively, our data reveal a critical but lineage-nonspecific role for pTalpha in mediating both allelic and isotypic exclusion in TCRbeta-transgenic mice.
Mots-clé
Alleles, Animals, Blotting, Western, Cell Lineage/immunology, Flow Cytometry, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, Genes, T-Cell Receptor beta, Hematopoietic Stem Cells/immunology, Hematopoietic Stem Cells/metabolism, Membrane Glycoproteins/genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptors, Antigen, T-Cell, alpha-beta/genetics, Receptors, Antigen, T-Cell, alpha-beta/metabolism, Reverse Transcriptase Polymerase Chain Reaction
Pubmed
Web of science
Création de la notice
09/02/2010 13:51
Dernière modification de la notice
20/08/2019 14:07
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