Longitudinal immunosequencing in healthy people reveals persistent T cell receptors rich in highly public receptors
Background: The adaptive immune system maintains a diversity of T cells capable of recognizing a broad array of antigens. Each T cell's specificity for antigens is determined by its T cell receptors (TCRs), which together across all T cells form a repertoire of millions of unique receptors in e...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2020
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| Online Access: | https://hdl.handle.net/1721.1/126457 |
| _version_ | 1826202663192100864 |
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| author | Chu, Nathaniel David Birnbaum, Michael E Alm, Eric J Bi, Haixin S |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Chu, Nathaniel David Birnbaum, Michael E Alm, Eric J Bi, Haixin S |
| author_sort | Chu, Nathaniel David |
| collection | MIT |
| description | Background: The adaptive immune system maintains a diversity of T cells capable of recognizing a broad array of antigens. Each T cell's specificity for antigens is determined by its T cell receptors (TCRs), which together across all T cells form a repertoire of millions of unique receptors in each individual. Although many studies have examined how TCR repertoires change in response to disease or drugs, few have explored the temporal dynamics of the TCR repertoire in healthy individuals. Results: Here we report immunosequencing of TCR β chains (TCRβ) from the blood of three healthy individuals at eight time points over one year. TCRβ repertoires of all peripheral-blood T cells and sorted memory T cells clustered clearly by individual, systematically demonstrating that TCRβ repertoires are specific to individuals across time. This individuality was absent from TCRβs from naive T cells, suggesting that the differences resulted from an individual's antigen exposure history, not genetic background. Many characteristics of the TCRβ repertoire (e.g., diversity, clonality) were stable across time, although we found evidence of T cell expansion dynamics even within healthy individuals. We further identified a subset of "persistent" TCRβs present across all time points. These receptors were rich in clonal and highly public receptors and may play a key role in immune system maintenance. Conclusions: Our results highlight the importance of longitudinal sampling of the immune system, providing a much-needed baseline for TCRβ dynamics in healthy individuals. Such a baseline will improve interpretation of changes in the TCRβ repertoire during disease or treatment. |
| first_indexed | 2024-09-23T12:13:05Z |
| format | Article |
| id | mit-1721.1/126457 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T12:13:05Z |
| publishDate | 2020 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1264572022-09-28T00:45:57Z Longitudinal immunosequencing in healthy people reveals persistent T cell receptors rich in highly public receptors Chu, Nathaniel David Birnbaum, Michael E Alm, Eric J Bi, Haixin S Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Microbiology Graduate Program Massachusetts Institute of Technology. Center for Microbiome Informatics and Therapeutics Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Civil and Environmental Engineering Background: The adaptive immune system maintains a diversity of T cells capable of recognizing a broad array of antigens. Each T cell's specificity for antigens is determined by its T cell receptors (TCRs), which together across all T cells form a repertoire of millions of unique receptors in each individual. Although many studies have examined how TCR repertoires change in response to disease or drugs, few have explored the temporal dynamics of the TCR repertoire in healthy individuals. Results: Here we report immunosequencing of TCR β chains (TCRβ) from the blood of three healthy individuals at eight time points over one year. TCRβ repertoires of all peripheral-blood T cells and sorted memory T cells clustered clearly by individual, systematically demonstrating that TCRβ repertoires are specific to individuals across time. This individuality was absent from TCRβs from naive T cells, suggesting that the differences resulted from an individual's antigen exposure history, not genetic background. Many characteristics of the TCRβ repertoire (e.g., diversity, clonality) were stable across time, although we found evidence of T cell expansion dynamics even within healthy individuals. We further identified a subset of "persistent" TCRβs present across all time points. These receptors were rich in clonal and highly public receptors and may play a key role in immune system maintenance. Conclusions: Our results highlight the importance of longitudinal sampling of the immune system, providing a much-needed baseline for TCRβ dynamics in healthy individuals. Such a baseline will improve interpretation of changes in the TCRβ repertoire during disease or treatment. 2020-07-31T11:44:53Z 2020-07-31T11:44:53Z 2019-06 2018-05 2020-03-04T16:00:22Z Article http://purl.org/eprint/type/JournalArticle 1471-2172 https://hdl.handle.net/1721.1/126457 Chu, Nathaniel D. et al. “Longitudinal immunosequencing in healthy people reveals persistent T cell receptors rich in highly public receptors.” BMC immunology, vol. 20, 2019, article 19 © 2019 The Author(s) en 10.1186/S12865-019-0300-5 BMC immunology Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC BioMed Central (BMC) |
| spellingShingle | Chu, Nathaniel David Birnbaum, Michael E Alm, Eric J Bi, Haixin S Longitudinal immunosequencing in healthy people reveals persistent T cell receptors rich in highly public receptors |
| title | Longitudinal immunosequencing in healthy people reveals persistent T cell receptors rich in highly public receptors |
| title_full | Longitudinal immunosequencing in healthy people reveals persistent T cell receptors rich in highly public receptors |
| title_fullStr | Longitudinal immunosequencing in healthy people reveals persistent T cell receptors rich in highly public receptors |
| title_full_unstemmed | Longitudinal immunosequencing in healthy people reveals persistent T cell receptors rich in highly public receptors |
| title_short | Longitudinal immunosequencing in healthy people reveals persistent T cell receptors rich in highly public receptors |
| title_sort | longitudinal immunosequencing in healthy people reveals persistent t cell receptors rich in highly public receptors |
| url | https://hdl.handle.net/1721.1/126457 |
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