Functionally specialized human CD4+ T-cell subsets express physicochemically distinct TCRs
The organizational integrity of the adaptive immune system is determined by functionally discrete subsets of CD4+ T cells, but it has remained unclear to what extent lineage choice is influenced by clonotypically expressed T-cell receptors (TCRs). To address this issue, we used a high-throughput app...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/57063 |
| _version_ | 1797997604529766400 |
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| author | Sofya A Kasatskaya Kristin Ladell Evgeniy S Egorov Kelly L Miners Alexey N Davydov Maria Metsger Dmitry B Staroverov Elena K Matveyshina Irina A Shagina Ilgar Z Mamedov Mark Izraelson Pavel V Shelyakin Olga V Britanova David A Price Dmitriy M Chudakov |
| author_facet | Sofya A Kasatskaya Kristin Ladell Evgeniy S Egorov Kelly L Miners Alexey N Davydov Maria Metsger Dmitry B Staroverov Elena K Matveyshina Irina A Shagina Ilgar Z Mamedov Mark Izraelson Pavel V Shelyakin Olga V Britanova David A Price Dmitriy M Chudakov |
| author_sort | Sofya A Kasatskaya |
| collection | DOAJ |
| description | The organizational integrity of the adaptive immune system is determined by functionally discrete subsets of CD4+ T cells, but it has remained unclear to what extent lineage choice is influenced by clonotypically expressed T-cell receptors (TCRs). To address this issue, we used a high-throughput approach to profile the αβ TCR repertoires of human naive and effector/memory CD4+ T-cell subsets, irrespective of antigen specificity. Highly conserved physicochemical and recombinatorial features were encoded on a subset-specific basis in the effector/memory compartment. Clonal tracking further identified forbidden and permitted transition pathways, mapping effector/memory subsets related by interconversion or ontogeny. Public sequences were largely confined to particular effector/memory subsets, including regulatory T cells (Tregs), which also displayed hardwired repertoire features in the naive compartment. Accordingly, these cumulative repertoire portraits establish a link between clonotype fate decisions in the complex world of CD4+ T cells and the intrinsic properties of somatically rearranged TCRs. |
| first_indexed | 2024-04-11T10:35:25Z |
| format | Article |
| id | doaj.art-1dd049e96e1b4c82816146e92ae81118 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:35:25Z |
| publishDate | 2020-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-1dd049e96e1b4c82816146e92ae811182022-12-22T04:29:18ZengeLife Sciences Publications LtdeLife2050-084X2020-12-01910.7554/eLife.57063Functionally specialized human CD4+ T-cell subsets express physicochemically distinct TCRsSofya A Kasatskaya0Kristin Ladell1Evgeniy S Egorov2Kelly L Miners3Alexey N Davydov4Maria Metsger5Dmitry B Staroverov6Elena K Matveyshina7https://orcid.org/0000-0003-4641-4906Irina A Shagina8Ilgar Z Mamedov9Mark Izraelson10Pavel V Shelyakin11Olga V Britanova12David A Price13https://orcid.org/0000-0001-9416-2737Dmitriy M Chudakov14https://orcid.org/0000-0003-0430-790XCenter of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russian Federation; Genomics of Adaptive Immunity Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian FederationDivision of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United KingdomGenomics of Adaptive Immunity Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian FederationDivision of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United KingdomAdaptive Immunity Group, Central European Institute of Technology, Brno, Czech RepublicAdaptive Immunity Group, Central European Institute of Technology, Brno, Czech RepublicGenomics of Adaptive Immunity Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation; Institute of Translational Medicine, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, Russian FederationFaculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russian FederationGenomics of Adaptive Immunity Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation; Institute of Translational Medicine, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, Russian FederationGenomics of Adaptive Immunity Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation; Institute of Translational Medicine, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, Russian FederationGenomics of Adaptive Immunity Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation; Institute of Translational Medicine, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, Russian FederationCenter of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russian Federation; Genomics of Adaptive Immunity Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian FederationGenomics of Adaptive Immunity Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation; Institute of Translational Medicine, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, Russian FederationDivision of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom; Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff, United KingdomCenter of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russian Federation; Genomics of Adaptive Immunity Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation; Institute of Translational Medicine, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, Russian FederationThe organizational integrity of the adaptive immune system is determined by functionally discrete subsets of CD4+ T cells, but it has remained unclear to what extent lineage choice is influenced by clonotypically expressed T-cell receptors (TCRs). To address this issue, we used a high-throughput approach to profile the αβ TCR repertoires of human naive and effector/memory CD4+ T-cell subsets, irrespective of antigen specificity. Highly conserved physicochemical and recombinatorial features were encoded on a subset-specific basis in the effector/memory compartment. Clonal tracking further identified forbidden and permitted transition pathways, mapping effector/memory subsets related by interconversion or ontogeny. Public sequences were largely confined to particular effector/memory subsets, including regulatory T cells (Tregs), which also displayed hardwired repertoire features in the naive compartment. Accordingly, these cumulative repertoire portraits establish a link between clonotype fate decisions in the complex world of CD4+ T cells and the intrinsic properties of somatically rearranged TCRs.https://elifesciences.org/articles/57063TCR repertoireCDR3 propertieshelper CD4+ subsetsplasticity of CD4+ subsets |
| spellingShingle | Sofya A Kasatskaya Kristin Ladell Evgeniy S Egorov Kelly L Miners Alexey N Davydov Maria Metsger Dmitry B Staroverov Elena K Matveyshina Irina A Shagina Ilgar Z Mamedov Mark Izraelson Pavel V Shelyakin Olga V Britanova David A Price Dmitriy M Chudakov Functionally specialized human CD4+ T-cell subsets express physicochemically distinct TCRs eLife TCR repertoire CDR3 properties helper CD4+ subsets plasticity of CD4+ subsets |
| title | Functionally specialized human CD4+ T-cell subsets express physicochemically distinct TCRs |
| title_full | Functionally specialized human CD4+ T-cell subsets express physicochemically distinct TCRs |
| title_fullStr | Functionally specialized human CD4+ T-cell subsets express physicochemically distinct TCRs |
| title_full_unstemmed | Functionally specialized human CD4+ T-cell subsets express physicochemically distinct TCRs |
| title_short | Functionally specialized human CD4+ T-cell subsets express physicochemically distinct TCRs |
| title_sort | functionally specialized human cd4 t cell subsets express physicochemically distinct tcrs |
| topic | TCR repertoire CDR3 properties helper CD4+ subsets plasticity of CD4+ subsets |
| url | https://elifesciences.org/articles/57063 |
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