High throughput sequencing reveals a complex pattern of dynamic interrelationships among human T cell subsets

QC 20150211
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.

Sanders, Catherine M. (författare)
Yang, Qunying (författare)
Schroeder, Harry W., Jr. (författare)
Wang, Elijah (författare)
Babrzadeh, FarbodStanford Genome Technology Center, United States(Swepub:kth)u1urz0h6 (författare)
Gharizadeh, Baback (författare)
Myers, Richard M. (författare)
Hudson, James R., Jr. (författare)
Davis, Ronald W. (författare)
Han, Jian (författare)
Stanford Genome Technology Center, United States (creator_code:org_t)

Ingår i:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences107:4, s. 1518-15230027-84241091-6490

Av författaren/redakt...: Wang, Chunlin; Sanders, Catheri ...; Yang, Qunying; Schroeder, Harry ...; Wang, Elijah; Babrzadeh, Farbo ...; visa fler...; Gharizadeh, Baba ...; Myers, Richard M ...; Hudson, James R. ...; Davis, Ronald W.; Han, Jian; visa färre...

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