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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Peptide library-based evaluation of T-cell receptor breadth detects defects in global and regulatory activation in human immunologic diseases
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Peptide library-based evaluation of T-cell receptor breadth detects defects in global and regulatory activation in human immunologic diseases

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

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摘要

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.

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