Peptide library-based evaluation of T-cell receptor breadth detects defects in global and regulatory activation in human immunologic diseases

Détails

ID Serval
serval:BIB_BF6A2C8F6B08
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Peptide library-based evaluation of T-cell receptor breadth detects defects in global and regulatory activation in human immunologic diseases
Périodique
Proc Natl Acad Sci U S A
Auteur(s)
Barber J. S., Yokomizo L. K., Sheikh V., Freeman A. F., Garabedian E., van Dijk E., Sokolic R., Candotti F., Weng N. P., Sereti I., Milner J. D.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
2013
Volume
110
Numéro
20
Pages
8164-9
Langue
anglais
Notes
Barber, John S
Yokomizo, Lauren K
Sheikh, Virginia
Freeman, Alexandra F
Garabedian, Elizabeth
van Dijk, Evert
Sokolic, Robert
Candotti, Fabio
Weng, Nan-ping
Sereti, Irini
Milner, Joshua D
eng
Intramural NIH HHS/
Research Support, N.I.H., Intramural
Proc Natl Acad Sci U S A. 2013 May 14;110(20):8164-9. doi: 10.1073/pnas.1302103110. Epub 2013 May 1.
Résumé
The ability of T-cells to respond to foreign antigens and to appropriately regulate this response is crucial for maintaining immune homeostasis. Using combinatorial peptide libraries, we functionally measured broad T-cell reactivity and observed impaired reactivity in established models of T-cell receptor repertoire restriction and in previously unrecognized disease contexts. By concurrently analyzing T-regulatory and T-effector cells, we show strong functional correlation between these subsets in healthy individuals and, strikingly, that alterations of this balance are associated with T helper type 2 (Th2)-mediated disease in a lymphopenic setting. Finally, we demonstrate that peptide-based priming of polyclonal naive cells with relatively low concentrations skews toward Th2 differentiation. These findings provide unique insight into the pathophysiology and functional consequences of abnormal T-cell repertoires and into differentiation of human naive T-cells.
Mots-clé
Antigens, CD14/metabolism, CD4-Positive T-Lymphocytes/cytology/*immunology, Cell Differentiation, Cell Proliferation, Cell Separation, Coculture Techniques, Flow Cytometry, *Gene Expression Regulation, Genes, MHC Class II, Humans, Immune System Diseases/immunology/metabolism, Leukocytes, Mononuclear/cytology/immunology, Lymphocyte Activation, Models, Statistical, *Peptide Library, Peptides/chemistry, Receptors, Antigen, T-Cell/*metabolism, T-Lymphocytes, Regulatory/cytology/immunology, Th2 Cells/cytology/immunology, atopy, immune deficiency
Pubmed
Open Access
Oui
Création de la notice
01/11/2017 11:29
Dernière modification de la notice
09/05/2019 0:39
Données d'usage