Intersection of population variation and autoimmunity genetics in human T cell activation
T lymphocyte activation by antigen conditions adaptive immune responses and immunopathologies, but we know little about its variation in humans and its genetic or environmental roots. We analyzed gene expression in CD4[superscript +] T cells during unbiased activation or in T helper 17 (T[subscript...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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American Association for the Advancement of Science (AAAS)
2016
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| Online Access: | http://hdl.handle.net/1721.1/105882 https://orcid.org/0000-0001-8567-2049 |
| _version_ | 1826214963490848768 |
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| author | Ye, C. J. Feng, T. Kwon, H.-K. Raj, T. Wilson, M. T. Asinovski, N. McCabe, C. Lee, M. H. Frohlich, I. Paik, H.-i. Zaitlen, N. Hacohen, N. Stranger, B. De Jager, P. Mathis, D. Benoist, C. Regev, Aviv |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Ye, C. J. Feng, T. Kwon, H.-K. Raj, T. Wilson, M. T. Asinovski, N. McCabe, C. Lee, M. H. Frohlich, I. Paik, H.-i. Zaitlen, N. Hacohen, N. Stranger, B. De Jager, P. Mathis, D. Benoist, C. Regev, Aviv |
| author_sort | Ye, C. J. |
| collection | MIT |
| description | T lymphocyte activation by antigen conditions adaptive immune responses and immunopathologies, but we know little about its variation in humans and its genetic or environmental roots. We analyzed gene expression in CD4[superscript +] T cells during unbiased activation or in T helper 17 (T[subscript H]17) conditions from 348 healthy participants representing European, Asian, and African ancestries. We observed interindividual variability, most marked for cytokine transcripts, with clear biases on the basis of ancestry, and following patterns more complex than simple T[subscript H]1/2/17 partitions. We identified 39 genetic loci specifically associated in cis with activated gene expression. We further fine-mapped and validated a single-base variant that modulates YY1 binding and the activity of an enhancer element controlling the autoimmune-associated IL2RA gene, affecting its activity in activated but not regulatory T cells. Thus, interindividual variability affects the fundamental immunologic process of T helper activation, with important connections to autoimmune disease. |
| first_indexed | 2024-09-23T16:13:59Z |
| format | Article |
| id | mit-1721.1/105882 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:13:59Z |
| publishDate | 2016 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1058822022-10-02T07:10:59Z Intersection of population variation and autoimmunity genetics in human T cell activation Ye, C. J. Feng, T. Kwon, H.-K. Raj, T. Wilson, M. T. Asinovski, N. McCabe, C. Lee, M. H. Frohlich, I. Paik, H.-i. Zaitlen, N. Hacohen, N. Stranger, B. De Jager, P. Mathis, D. Benoist, C. Regev, Aviv Massachusetts Institute of Technology. Department of Biology Regev, Aviv T lymphocyte activation by antigen conditions adaptive immune responses and immunopathologies, but we know little about its variation in humans and its genetic or environmental roots. We analyzed gene expression in CD4[superscript +] T cells during unbiased activation or in T helper 17 (T[subscript H]17) conditions from 348 healthy participants representing European, Asian, and African ancestries. We observed interindividual variability, most marked for cytokine transcripts, with clear biases on the basis of ancestry, and following patterns more complex than simple T[subscript H]1/2/17 partitions. We identified 39 genetic loci specifically associated in cis with activated gene expression. We further fine-mapped and validated a single-base variant that modulates YY1 binding and the activity of an enhancer element controlling the autoimmune-associated IL2RA gene, affecting its activity in activated but not regulatory T cells. Thus, interindividual variability affects the fundamental immunologic process of T helper activation, with important connections to autoimmune disease. 2016-12-19T21:32:34Z 2016-12-19T21:32:34Z 2014-09 2014-04 Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 http://hdl.handle.net/1721.1/105882 Ye, C. J. et al. “Intersection of Population Variation and Autoimmunity Genetics in Human T Cell Activation.” Science 345.6202 (2014): 1254665–1254665. https://orcid.org/0000-0001-8567-2049 en_US http://dx.doi.org/10.1126/science.1254665 Science Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Ye, C. J. Feng, T. Kwon, H.-K. Raj, T. Wilson, M. T. Asinovski, N. McCabe, C. Lee, M. H. Frohlich, I. Paik, H.-i. Zaitlen, N. Hacohen, N. Stranger, B. De Jager, P. Mathis, D. Benoist, C. Regev, Aviv Intersection of population variation and autoimmunity genetics in human T cell activation |
| title | Intersection of population variation and autoimmunity genetics in human T cell activation |
| title_full | Intersection of population variation and autoimmunity genetics in human T cell activation |
| title_fullStr | Intersection of population variation and autoimmunity genetics in human T cell activation |
| title_full_unstemmed | Intersection of population variation and autoimmunity genetics in human T cell activation |
| title_short | Intersection of population variation and autoimmunity genetics in human T cell activation |
| title_sort | intersection of population variation and autoimmunity genetics in human t cell activation |
| url | http://hdl.handle.net/1721.1/105882 https://orcid.org/0000-0001-8567-2049 |
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