title: High throughput sequencing reveals a complex pattern of dynamic interrelationships among human T cell subsets.
abstract: 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.
authors.affiliation: Stanford Genome Technology Center, Palo Alto, CA 94304, USA.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Wang
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Sanders
authors.forename: Qunying
authors.initials: Q
authors.lastname: Yang
authors.forename: Harry W
authors.initials: HW
authors.lastname: Schroeder
authors.forename: Elijah
authors.initials: E
authors.lastname: Wang
authors.forename: Farbod
authors.initials: F
authors.lastname: Babrzadeh
authors.forename: Baback
authors.initials: B
authors.lastname: Gharizadeh
authors.forename: Richard M
authors.initials: RM
authors.lastname: Myers
authors.forename: James R
authors.initials: JR
authors.lastname: Hudson
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Davis
authors.forename: Jian
authors.initials: J
authors.lastname: Han
mesh_terms: D000595:Amino Acid Sequence; D002454:Cell Differentiation; D019070:Cell Lineage; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000166:cytology / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell