High throughput sequencing reveals a complex pattern of dynamic interrelationships among human T cell subsets.
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.
Wang
Chunlin
C
Stanford Genome Technology Center, Palo Alto, CA 94304, USA.
Sanders
Catherine M
CM
Yang
Qunying
Q
Schroeder
Harry W
HW
Wang
Elijah
E
Babrzadeh
Farbod
F
Gharizadeh
Baback
B
Myers
Richard M
RM
Hudson
James R
JR
Davis
Ronald W
RW
Han
Jian
J
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*
D011948:Receptors, Antigen, T-Cell