Diversity and clonal selection in the human T-cell repertoire

T-cell receptor (TCR) diversity, a prerequisite for immune system recognition of the universe of foreign antigens, is generated in the first two decades of life in the thymus and then persists to an unknown extent through life via homeostatic proliferation of naïve T cells. We have used next-generation sequencing and nonparametric statistical analysis to estimate a lower bound for the total number of different TCR beta (TCRB) sequences in human repertoires. We arrived at surprisingly high minimal estimates of 100 million unique TCRB sequences in naïve CD4 and CD8 T-cell repertoires of young adults. Naïve repertoire richness modestly declined two- to fivefold in healthy elderly. Repertoire richness contraction…

• EM
  Ellison Medical Foundation
• NT
  National Tsing Hua University
• NI
  National Institutes of Health

  Awards: AI057266, AI044142, R01 AG015043, R01 AI108891, AR042527, R01 AR042527, AI108891, P01 HL058000, HL058000, U19 AI057266, U19 AI090019, AI090019, R01 AI044142