Human invariant V alpha 24-J alpha Q TCR supports the development of CD1d-dependent NK1.1+ and NK1.1- T cells in transgenic mice.

Détails

ID Serval
serval:BIB_27994
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Human invariant V alpha 24-J alpha Q TCR supports the development of CD1d-dependent NK1.1+ and NK1.1- T cells in transgenic mice.
Périodique
Journal of immunology
Auteur⸱e⸱s
Capone M., Cantarella D., Schümann J., Naidenko O.V., Garavaglia C., Beermann F., Kronenberg M., Dellabona P., MacDonald H.R., Casorati G.
ISSN
0022-1767
Statut éditorial
Publié
Date de publication
2003
Peer-reviewed
Oui
Volume
170
Numéro
5
Pages
2390-2398
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Résumé
A sizable fraction of T cells expressing the NK cell marker NK1.1 (NKT cells) bear a very conserved TCR, characterized by homologous invariant (inv.) TCR V alpha 24-J alpha Q and V alpha 14-J alpha 18 rearrangements in humans and mice, respectively, and are thus defined as inv. NKT cells. Because human inv. NKT cells recognize mouse CD1d in vitro, we wondered whether a human inv. V alpha 24 TCR could be selected in vivo by mouse ligands presented by CD1d, thereby supporting the development of inv. NKT cells in mice. Therefore, we generated transgenic (Tg) mice expressing the human inv. V alpha 24-J alpha Q TCR chain in all T cells. The expression of the human inv. V alpha 24 TCR in TCR C alpha(-/-) mice indeed rescues the development of inv. NKT cells, which home preferentially to the liver and respond to the CD1d-restricted ligand alpha-galactosylceramide (alpha-GalCer). However, unlike inv. NKT cells from non-Tg mice, the majority of NKT cells in V alpha 24 Tg mice display a double-negative phenotype, as well as a significant increase in TCR V beta 7 and a corresponding decrease in TCR V beta 8.2 use. Despite the forced expression of the human CD1d-restricted TCR in C alpha(-/-) mice, staining with mCD1d-alpha-GalCer tetramers reveals that the absolute numbers of peripheral CD1d-dependent T lymphocytes increase at most by 2-fold. This increase is accounted for mainly by an increased fraction of NK1.1(-) T cells that bind CD1d-alpha-GalCer tetramers. These findings indicate that human inv. V alpha 24 TCR supports the development of CD1d-dependent lymphocytes in mice, and argue for a tight homeostatic control on the total number of inv. NKT cells. Thus, human inv. V alpha 24 TCR-expressing mice are a valuable model to study different aspects of the inv. NKT cell subset.
Mots-clé
Animals, Antigens/biosynthesis, Antigens, CD1/physiology, Antigens, CD1d, Antigens, Differentiation, B-Lymphocyte/biosynthesis, Antigens, Differentiation, B-Lymphocyte/genetics, Antigens, Ly, Antigens, Surface, Cell Differentiation/genetics, Cell Differentiation/immunology, Cells, Cultured, Epitopes, T-Lymphocyte/immunology, Galactosylceramides/immunology, Gene Expression Regulation/genetics, Gene Expression Regulation/immunology, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor/genetics, Genes, T-Cell Receptor alpha/genetics, Genes, T-Cell Receptor alpha/physiology, Histocompatibility Antigens Class II/biosynthesis, Histocompatibility Antigens Class II/genetics, Humans, Immunoglobulin Constant Regions/genetics, Immunophenotyping, Killer Cells, Natural/cytology, Killer Cells, Natural/immunology, Lectins, C-Type, Lymphocyte Count, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Knockout, Mice, Transgenic/immunology, NK Cell Lectin-Like Receptor Subfamily B, Protein Biosynthesis, Proteins, Receptors, Antigen, T-Cell, alpha-beta/biosynthesis, Receptors, Antigen, T-Cell, alpha-beta/deficiency, T-Lymphocyte Subsets/cytology, T-Lymphocyte Subsets/immunology
Pubmed
Web of science
Création de la notice
19/11/2007 13:24
Dernière modification de la notice
20/08/2019 14:06
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