Self-mediated positive selection of T cells sets an obstacle to the recognition of nonself
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...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2021
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| Sorozat: | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
118 No. 37 |
| Tárgyszavak: | |
| doi: | 10.1073/pnas.2100542118 |
| mtmt: | 32235619 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/22479 |
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| 024 | 7 | |a 32235619 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
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| 100 | 1 | |a Koncz Balázs | |
| 245 | 1 | 0 | |a Self-mediated positive selection of T cells sets an obstacle to the recognition of nonself |h [elektronikus dokumentum] / |c Koncz Balázs |
| 260 | |c 2021 | ||
| 300 | |a Terjedelem: 11-Azonosító: e2100542118 | ||
| 490 | 0 | |a PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA |v 118 No. 37 | |
| 520 | 3 | |a 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. © 2021 National Academy of Sciences. All rights reserved. | |
| 650 | 4 | |a Biológiai tudományok | |
| 650 | 4 | |a Klinikai orvostan | |
| 700 | 0 | 1 | |a Balogh Gergő Mihály |e aut |
| 700 | 0 | 1 | |a Papp Benjamin Tamás |e aut |
| 700 | 0 | 1 | |a Asztalos Leó |e aut |
| 700 | 0 | 1 | |a Kemény Lajos |e aut |
| 700 | 0 | 1 | |a Manczinger Máté |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/22479/1/e2100542118.full.pdf |z Dokumentum-elérés |