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Thymus-derived regulatory T cells are positively selected on natural self-antigen through cognate interactions of high functional avidity

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Item Type:Article
Title:Thymus-derived regulatory T cells are positively selected on natural self-antigen through cognate interactions of high functional avidity
Creators Name:Kieback, E. and Hilgenberg, E. and Stervbo, U. and Lampropoulou, V. and Shen, P. and Bunse, M. and Jaimes, Y. and Boudinot, P. and Radbruch, A. and Klemm, U. and Kuehl, A.A. and Liblau, R. and Hoevelmeyer, N. and Anderton, S.M. and Uckert, W. and Fillatreau, S.
Abstract:Regulatory T (Treg) cells expressing Foxp3 transcripton factor are essential for immune homeostasis. They arise in the thymus as a separate lineage from conventional CD4(+)Foxp3(-) T (Tconv) cells. Here, we show that the thymic development of Treg cells depends on the expression of their endogenous cognate self-antigen. The formation of these cells was impaired in mice lacking this self-antigen, while Tconv cell development was not negatively affected. Thymus-derived Treg cells were selected by self-antigens in a specific manner, while autoreactive Tconv cells were produced through degenerate recognition of distinct antigens. These distinct modes of development were associated with the expression of T cell receptor of higher functional avidity for self-antigen by Treg cells than Tconv cells, a difference subsequently essential for the control of autoimmunity. Our study documents how self-antigens define the repertoire of thymus-derived Treg cells to subsequently endow this cell type with the capacity to undermine autoimmune attack.
Keywords:Autoantigens, CTLA-4 Antigen, Cultured Cells, Antigen-Mediated Clonal Selection, Experimental Autoimmune Encephalomyelitis, Forkhead Transcription Factors, Inbred C57BL Mice, Knockout Mice, Multiple Sclerosis, Myelin-Oligodendrocyte Glycoprotein, Peptide Fragments, T-Cell Antigen Receptors, T-Cell Antigen Receptor Specificity, T-Lymphocyte Subsets, Regulatory T-Lymphocytes, Thymus Gland, Animals, Mice
Source:Immunity
ISSN:1074-7613
Publisher:Cell Press / Elsevier (U.S.A.)
Volume:44
Number:5
Page Range:1114-1126
Date:17 May 2016
Official Publication:https://doi.org/10.1016/j.immuni.2016.04.018
PubMed:View item in PubMed

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