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Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets

It is well known that the most important feature of adaptive immunity is the specificity that provides highly precise recognition of the self, altered-self, and non-self. Due to the high specificity of antigen recognition, the adaptive immune system participates in the maintenance of genetic homeost...

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Autores principales: Shevyrev, Daniil, Tereshchenko, Valeriy, Kozlov, Vladimir, Sennikov, Sergey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773594/
https://www.ncbi.nlm.nih.gov/pubmed/35053310
http://dx.doi.org/10.3390/cells11020194
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author Shevyrev, Daniil
Tereshchenko, Valeriy
Kozlov, Vladimir
Sennikov, Sergey
author_facet Shevyrev, Daniil
Tereshchenko, Valeriy
Kozlov, Vladimir
Sennikov, Sergey
author_sort Shevyrev, Daniil
collection PubMed
description It is well known that the most important feature of adaptive immunity is the specificity that provides highly precise recognition of the self, altered-self, and non-self. Due to the high specificity of antigen recognition, the adaptive immune system participates in the maintenance of genetic homeostasis, supports multicellularity, and protects an organism from different pathogens at a qualitatively different level than innate immunity. This seemingly simple property is based on millions of years of evolution that led to the formation of diversification mechanisms of antigen-recognizing receptors and later to the emergence of a system of presentation of the self and non-self antigens. The latter could have a crucial significance because the presentation of nearly complete diversity of auto-antigens in the thymus allows for the “calibration” of the forming repertoires of T-cells for the recognition of self, altered-self, and non-self antigens that are presented on the periphery. The central role in this process belongs to promiscuous gene expression by the thymic epithelial cells that express nearly the whole spectrum of proteins encoded in the genome, meanwhile maintaining their cellular identity. This complex mechanism requires strict control that is executed by several transcription factors. One of the most important of them is AIRE. This noncanonical transcription factor not only regulates the processes of differentiation and expression of peripheral tissue-specific antigens in the thymic medullar epithelial cells but also controls intercellular interactions in the thymus. Besides, it participates in an increase in the diversity and transfer of presented antigens and thus influences the formation of repertoires of maturing thymocytes. Due to these complex effects, AIRE is also called a transcriptional regulator. In this review, we briefly described the history of AIRE discovery, its structure, functions, and role in the formation of antigen-recognizing receptor repertoires, along with other transcription factors. We focused on the phylogenetic prerequisites for the development of modern adaptive immunity and emphasized the importance of the antigen presentation system.
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spelling pubmed-87735942022-01-21 Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets Shevyrev, Daniil Tereshchenko, Valeriy Kozlov, Vladimir Sennikov, Sergey Cells Review It is well known that the most important feature of adaptive immunity is the specificity that provides highly precise recognition of the self, altered-self, and non-self. Due to the high specificity of antigen recognition, the adaptive immune system participates in the maintenance of genetic homeostasis, supports multicellularity, and protects an organism from different pathogens at a qualitatively different level than innate immunity. This seemingly simple property is based on millions of years of evolution that led to the formation of diversification mechanisms of antigen-recognizing receptors and later to the emergence of a system of presentation of the self and non-self antigens. The latter could have a crucial significance because the presentation of nearly complete diversity of auto-antigens in the thymus allows for the “calibration” of the forming repertoires of T-cells for the recognition of self, altered-self, and non-self antigens that are presented on the periphery. The central role in this process belongs to promiscuous gene expression by the thymic epithelial cells that express nearly the whole spectrum of proteins encoded in the genome, meanwhile maintaining their cellular identity. This complex mechanism requires strict control that is executed by several transcription factors. One of the most important of them is AIRE. This noncanonical transcription factor not only regulates the processes of differentiation and expression of peripheral tissue-specific antigens in the thymic medullar epithelial cells but also controls intercellular interactions in the thymus. Besides, it participates in an increase in the diversity and transfer of presented antigens and thus influences the formation of repertoires of maturing thymocytes. Due to these complex effects, AIRE is also called a transcriptional regulator. In this review, we briefly described the history of AIRE discovery, its structure, functions, and role in the formation of antigen-recognizing receptor repertoires, along with other transcription factors. We focused on the phylogenetic prerequisites for the development of modern adaptive immunity and emphasized the importance of the antigen presentation system. MDPI 2022-01-07 /pmc/articles/PMC8773594/ /pubmed/35053310 http://dx.doi.org/10.3390/cells11020194 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Shevyrev, Daniil
Tereshchenko, Valeriy
Kozlov, Vladimir
Sennikov, Sergey
Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets
title Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets
title_full Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets
title_fullStr Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets
title_full_unstemmed Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets
title_short Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets
title_sort phylogeny, structure, functions, and role of aire in the formation of t-cell subsets
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773594/
https://www.ncbi.nlm.nih.gov/pubmed/35053310
http://dx.doi.org/10.3390/cells11020194
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