High throughput sequencing reveals a complex pattern of dynamic interrelationships among human T cell subsets
2010 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, no 4, 1518-1523 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2010. Vol. 107, no 4, 1518-1523 p.
CDR3, clonal expansion, immune repertoire, T cell receptor
IdentifiersURN: urn:nbn:se:kth:diva-159904DOI: 10.1073/pnas.0913939107ISI: 000273974600053PubMedID: 20080641ScopusID: 2-s2.0-76549090763OAI: oai:DiVA.org:kth-159904DiVA: diva2:787660
QC 201502112015-02-112015-02-112015-02-11Bibliographically approved