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

Authors:
Barber JS1, Yokomizo LK, Sheikh V, Freeman AF, Garabedian E, van Dijk E, Sokolic R, Candotti F, Weng NP, Sereti I, Milner JD.
In:
Source: Proc Natl Acad Sci USA
Publication Date: (2013)
Issue: 110(20): 8164-9
Research Area:
Immunotherapy / Hematology
Basic Research
Culture Media:
Experiment


Abstract

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.