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Fohse, L.* ; Suffner, J.* ; Suhre, K. ; Wahl, B.* ; Lindner, C.* ; Lee, C.W.* ; Schmitz, S.* ; Haas, J.D.* ; Lamprecht, S.* ; Koenecke, C.* ; Bleich, A.* ; Hämmerling, G.J.* ; Malissen, B.* ; Suerbaum, S.* ; Forster, R.* ; Prinz, I.

High TCR diversity ensures optimal function and homeostasis of Foxp3+ regulatory T cells.

Eur. J. Immunol. 41, 3101-3113 (2011)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Dominant tolerance to self-antigen requires the presence of sufficient numbers of CD4(+) Foxp3(+) Treg cells with matching antigen specificity. However, the size and role of TCR repertoire diversity for antigen-specific immuno-regulation through Treg cells is not clear. Here, we developed and applied a novel high-throughput (HT) TCR sequencing approach to analyze the TCR repertoire of Treg cells and revealed the importance of high diversity for Treg-cell homeostasis and function. We found that highly polyclonal Treg cells from WT mice vigorously expanded after adoptive transfer into non-lymphopenic TCR-transgenic recipients with low Treg-cell diversity. In that system, we identified specific Treg-cell TCR preferences in distinct anatomic locations such as the mesenteric LN indicating that Treg cells continuously compete for MHC class-II-presented self-, food-, or flora-antigen. Functionally, we showed that high TCR diversity was required for optimal suppressive function of Treg cells in experimental acute graft versus host disease (GvHD). In conclusion, we suggest that efficient immuno-regulation by Treg cells requires high TCR diversity. Thereby, continuous competition of peripheral Treg cells for limited self-antigen shapes an organ-optimized, yet highly diverse, local TCR repertoire.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Experimental GvHD; Foxp3; High-throughput sequencing; TCR repertoire; Treg cells; Treg-homeostasis
ISSN (print) / ISBN 0014-2980
e-ISSN 1521-4141
Journal European Journal of Immunology
Quellenangaben Volume: 41, Issue: 11, Pages: 3101-3113 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Reviewing status Peer reviewed
Institute(s) Institute of Bioinformatics and Systems Biology (IBIS)