Early life imprints the hierarchy of T cell clone sizes
The adaptive immune system responds to pathogens by selecting clones of cells with specific receptors. While clonal selection in response to particular antigens has been studied in detail, it is unknown how a lifetime of exposures to many antigens collectively shape the immune repertoire. Here, usin...
| 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 |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/61639 |
| _version_ | 1811200414531452928 |
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| author | Mario U Gaimann Maximilian Nguyen Jonathan Desponds Andreas Mayer |
| author_facet | Mario U Gaimann Maximilian Nguyen Jonathan Desponds Andreas Mayer |
| author_sort | Mario U Gaimann |
| collection | DOAJ |
| description | The adaptive immune system responds to pathogens by selecting clones of cells with specific receptors. While clonal selection in response to particular antigens has been studied in detail, it is unknown how a lifetime of exposures to many antigens collectively shape the immune repertoire. Here, using mathematical modeling and statistical analyses of T cell receptor sequencing data, we develop a quantitative theory of human T cell dynamics compatible with the statistical laws of repertoire organization. We find that clonal expansions during a perinatal time window leave a long-lasting imprint on the human T cell repertoire, which is only slowly reshaped by fluctuating clonal selection during adult life. Our work provides a mechanism for how early clonal dynamics imprint the hierarchy of T cell clone sizes with implications for pathogen defense and autoimmunity. |
| first_indexed | 2024-04-12T02:03:06Z |
| format | Article |
| id | doaj.art-11464cb9fec948e897da8fa6d6fc036b |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:03:06Z |
| publishDate | 2020-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-11464cb9fec948e897da8fa6d6fc036b2022-12-22T03:52:36ZengeLife Sciences Publications LtdeLife2050-084X2020-12-01910.7554/eLife.61639Early life imprints the hierarchy of T cell clone sizesMario U Gaimann0https://orcid.org/0000-0002-2789-090XMaximilian Nguyen1https://orcid.org/0000-0002-4378-5050Jonathan Desponds2https://orcid.org/0000-0001-7112-3217Andreas Mayer3https://orcid.org/0000-0002-6643-7622Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States; Arnold Sommerfeld Center for Theoretical Physics and Center for NanoScience, Department of Physics, Ludwig-Maximilians-Universität München, München, GermanyLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United StatesNSF-Simons Center for Quantitative Biology, Northwestern University, Evanston, United StatesLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United StatesThe adaptive immune system responds to pathogens by selecting clones of cells with specific receptors. While clonal selection in response to particular antigens has been studied in detail, it is unknown how a lifetime of exposures to many antigens collectively shape the immune repertoire. Here, using mathematical modeling and statistical analyses of T cell receptor sequencing data, we develop a quantitative theory of human T cell dynamics compatible with the statistical laws of repertoire organization. We find that clonal expansions during a perinatal time window leave a long-lasting imprint on the human T cell repertoire, which is only slowly reshaped by fluctuating clonal selection during adult life. Our work provides a mechanism for how early clonal dynamics imprint the hierarchy of T cell clone sizes with implications for pathogen defense and autoimmunity.https://elifesciences.org/articles/61639immune repertoirepower-law scalingimprintingT cell immunityrepertoire sequencingfluctuating fitness |
| spellingShingle | Mario U Gaimann Maximilian Nguyen Jonathan Desponds Andreas Mayer Early life imprints the hierarchy of T cell clone sizes eLife immune repertoire power-law scaling imprinting T cell immunity repertoire sequencing fluctuating fitness |
| title | Early life imprints the hierarchy of T cell clone sizes |
| title_full | Early life imprints the hierarchy of T cell clone sizes |
| title_fullStr | Early life imprints the hierarchy of T cell clone sizes |
| title_full_unstemmed | Early life imprints the hierarchy of T cell clone sizes |
| title_short | Early life imprints the hierarchy of T cell clone sizes |
| title_sort | early life imprints the hierarchy of t cell clone sizes |
| topic | immune repertoire power-law scaling imprinting T cell immunity repertoire sequencing fluctuating fitness |
| url | https://elifesciences.org/articles/61639 |
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