Shaping of the autoreactive T-cell repertoire by a splice variant of self protein expressed in thymic epithelial cells

10.1038/71540 ◽  
2000 ◽  
Vol 6 (1) ◽  
pp. 56-61 ◽  
Author(s):  
Ludger Klein ◽  
Matthias Klugmann ◽  
Klaus-Armin Nave ◽  
V K Tuohy ◽  
Bruno Kyewski
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Splice Variant ◽  
Thymic Epithelial Cells ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Autoreactive T Cell

scholarly journals The Aire family expands

2019 ◽  
Vol 216 (5) ◽  
pp. 1010-1011
Author(s):  
Adrian Liston ◽  
James Dooley
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Lymph Nodes ◽  
Thymic Epithelial Cells ◽  
T Cell Tolerance ◽  
T Cell Repertoire ◽  
Cell Tolerance ◽  
Cell Repertoire

T cell tolerance depends upon Aire-expressing cells to purge the T cell repertoire of autoreactive clones. Once thought to be the exclusive domain of thymic epithelial cells, a new study by Yamano et al. (https://doi.org/10.1084/jem.20181430) in this issue of JEM identifies ILC3-like cells in the lymph nodes with similar properties.

scholarly journals Self-mediated positive selection of T cells sets an obstacle to the recognition of nonself

2021 ◽  
Vol 118 (37) ◽  
pp. e2100542118
Author(s):  
Balázs Koncz ◽  
Gergő M. Balogh ◽  
Benjamin T. Papp ◽  
Leó Asztalos ◽  
Lajos Kemény ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Epithelial Cells ◽  
Positive Selection ◽  
Thymic Epithelial Cells ◽  
Immune Recognition ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Adaptive Immune ◽  
Selection Of

Adaptive immune recognition is mediated by the binding of peptide–human leukocyte antigen complexes by T cells. Positive selection of T cells in the thymus is a fundamental step in the generation of a responding T cell repertoire: only those T cells survive that recognize human peptides presented on the surface of cortical thymic epithelial cells. We propose that while this step is essential for optimal immune function, the process results in a defective T cell repertoire because it is mediated by self-peptides. To test our hypothesis, we focused on amino acid motifs of peptides in contact with T cell receptors. We found that motifs rarely or not found in the human proteome are unlikely to be recognized by the immune system just like the ones that are not expressed in cortical thymic epithelial cells or not presented on their surface. Peptides carrying such motifs were especially dissimilar to human proteins. Importantly, we present our main findings on two independent T cell activation datasets and directly demonstrate the absence of naïve T cells in the repertoire of healthy individuals. We also show that T cell cross-reactivity is unable to compensate for the absence of positively selected T cells. Additionally, we show that the proposed mechanism could influence the risk for different infectious diseases. In sum, our results suggest a side effect of T cell positive selection, which could explain the nonresponsiveness to many nonself peptides and could improve the understanding of adaptive immune recognition.

scholarly journals NF‐κB‐inducing kinase contributes to normal development of cortical thymic epithelial cells: its possible role in shaping a proper T‐cell repertoire

Immunology ◽  
2020 ◽  
Vol 160 (2) ◽  
pp. 198-208
Author(s):  
Koji Eshima ◽  
Kana Misawa ◽  
Chihiro Ohashi ◽  
Haruka Noma ◽  
Kazuya Iwabuchi
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Normal Development ◽  
Thymic Epithelial Cells ◽  
T Cell Repertoire ◽  
Cell Repertoire

scholarly journals Expression of a Natural Tumor Antigen by Thymic Epithelial Cells Impairs the Tumor-Protective CD4+ T-Cell Repertoire

2005 ◽  
Vol 65 (14) ◽  
pp. 6443-6449 ◽  
Author(s):  
Rinke Bos ◽  
Suzanne van Duikeren ◽  
Thorbald van Hall ◽  
Patricia Kaaijk ◽  
Richard Taubert ◽  
...  
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Tumor Antigen ◽  
Cd4 T Cell ◽  
Thymic Epithelial Cells ◽  
T Cell Repertoire ◽  
Cell Repertoire

scholarly journals The target cell response to cytokines governs the autoreactive T cell repertoire in the pancreas of NOD mice

Diabetologia ◽  
2008 ◽  
Vol 52 (2) ◽  
pp. 299-305 ◽  
Author(s):  
M. Hultcrantz ◽  
S. Jacobson ◽  
N. J. Hill ◽  
P. Santamaria ◽  
M. Flodström-Tullberg
Keyword(s):  
T Cell ◽  
Target Cell ◽  
Cell Response ◽  
Nod Mice ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Autoreactive T Cell

scholarly journals HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis

Cell ◽  
2020 ◽  
Vol 183 (5) ◽  
pp. 1264-1281.e20 ◽  
Author(s):  
Jian Wang ◽  
Ivan Jelcic ◽  
Lena Mühlenbruch ◽  
Veronika Haunerdinger ◽  
Nora C. Toussaint ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Autoreactive T Cell

Cell components required for deletion of an autoreactive T cell repertoire

1990 ◽  
Vol 20 (5) ◽  
pp. 1153-1160 ◽  
Author(s):  
Noriko Fukushi ◽  
Bingyan Wang ◽  
Hisashi Arase ◽  
Kazumasa Ogasawara ◽  
Robert A. Good ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Autoreactive T Cell ◽  
Cell Components

scholarly journals Doxycycline Protects Thymic Epithelial Cells from Mitomycin C-Mediated Apoptosis In Vitro via Trx2-NF-κB-Bcl-2/Bax Axis

2016 ◽  
Vol 38 (2) ◽  
pp. 449-460 ◽  
Author(s):  
Jun Wang ◽  
Ya Zhuo ◽  
Lei Yin ◽  
Hui Wang ◽  
Yanqiu Jiang ◽  
...  
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Mitomycin C ◽  
Mapk Signaling ◽  
Thymic Epithelial Cells ◽  
Cell Repertoire ◽  
Gm Csf ◽  
Induced Apoptosis ◽  
A Tec

Background/Aims: Age-associated and stress-induced involution of the thymus is accompanied by reduced numbers of thymic epithelial cells (TECs) and severe reduction in peripheral T cell repertoire specificities. These events seriously affect immune function, but the mechanisms involved are unclear. Our preliminary findings showed that doxycycline (Dox) could drive the proliferation of a TEC line (MTEC1 cells) partially via the MAPK signaling pathway. Dox can also up-regulate IL-6 and GM-CSF expression via the NF-κB and MAPK/ERK pathways. Herein, we investigate the effects and mechanisms used by Dox that protect against mitomycin C (MMC)-induced MTEC1 cell apoptosis. Methods: MTEC1 cells were treated with Dox, MMC, and Dox plus MMC for different amounts of time. The expression of Trx2, NF-κB, Bcl-2, and Bax proteins were then detected by western blotting. Results: Our findings show that Dox protects MTEC1 cells from MMC-induced apoptosis. Dox up-regulated the expression of Trx2 and promoted NF-κB phosphorylation. Meanwhile, Dox also increased the expression of Bcl-2, partially reduced the expression of Bax, and normalized the ratio of Bcl-2 to Bax. Conclusion: Dox exerts an anti-apoptosis function via the NF-κB-Bcl-2/Bax and Trx2-ASK1/JNK pathways in vitro. Therefore, Dox may represent a drug that could be used to attenuate thymic senescence, rescue thymic function, and promote T cell reconstitution.

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