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High throughput sequencing reveals a complex pattern of dynamic interrelationships among human T cell subsets
- Wang, Chunlin (author)
- Sanders, Catherine M. (author)
- Yang, Qunying (author)
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- Schroeder, Harry W., Jr. (author)
- Wang, Elijah (author)
- Gharizadeh, Baback (author)
- Myers, Richard M. (author)
- Hudson, James R., Jr. (author)
- Davis, Ronald W. (author)
- Han, Jian (author)
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- (creator_code:org_t)
- 2010-01-04
- 2010
- English.
- In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:4, s. 1518-1523
- Journal article (peer-reviewed)
Abstract
Subject headings
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- Developing T cells face a series of cell fate choices in the thymus and in the periphery. The role of the individual T cell receptor (TCR) in determining decisions of cell fate remains unresolved. The stochastic/selection model postulates that the initial fate of the cell is independent of TCR specificity, with survival dependent on additional TCR/coreceptor "rescue" signals. The "instructive" model holds that cell fate is initiated by the interaction of the TCR with a cognate peptide-MHC complex. T cells are then segregated on the basis of TCR specificity with the aid of critical coreceptors and signal modulators [Chan S, Correia-Neves M, Benoist C, Mathis (1998) Immunol Rev 165: 195-207]. The former would predict a random representation of individual TCR across divergent T cell lineages whereas the latter would predict minimal overlap between divergent T cell subsets. To address this issue, we have used high-throughput sequencing to evaluate the TCR distribution among key T cell developmental and effector subsets from a single donor. We found numerous examples of individual subsets sharing identical TCR sequence, supporting a model of a stochastic process of cell fate determination coupled with dynamic patterns of clonal expansion of T cells bearing the same TCR sequence among both CD4(+) and CD8+ populations.
Subject headings
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
Keyword
- CDR3
- clonal expansion
- immune repertoire
- T cell receptor
Publication and Content Type
- ref (subject category)
- art (subject category)
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