Peptide library-based evaluation of T-cell receptor breadth detects defects in global and regulatory activation in human immunologic diseases
| Autor: | Nan-ping Weng, Elizabeth Garabedian, Irini Sereti, Evert van Dijk, Lauren K. Yokomizo, Fabio Candotti, Virginia Sheikh, John S. Barber, Robert A. Sokolic, Joshua D. Milner, Alexandra F. Freeman |
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| Rok vydání: | 2013 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cellular differentiation Genes MHC Class II Lipopolysaccharide Receptors Receptors Antigen T-Cell Priming (immunology) Cell Separation Disease Biology Lymphocyte Activation T-Lymphocytes Regulatory Th2 Cells Antigen Peptide Library Humans Peptide library Cell Proliferation Regulation of gene expression Models Statistical Multidisciplinary Cell growth T-cell receptor Cell Differentiation Biological Sciences Flow Cytometry Coculture Techniques Gene Expression Regulation Immune System Diseases Immunology Leukocytes Mononuclear Peptides |
| Zdroj: | Proceedings of the National Academy of Sciences. 110:8164-8169 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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