Intersection of population variation and autoimmunity genetics in human T cell activation
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Regev_Intersection of population.pdf
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2.6 MB
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Checksum (MD5)
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Author(s)
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.
Date Issued
September 2014
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Ye, C. J. et al. “Intersection of Population Variation and Autoimmunity Genetics in Human T Cell Activation.” Science 345.6202 (2014): 1254665–1254665.
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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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.
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DOI of Published Version
https://doi.org/10.1126/science.1254665
