Naive CD8⁺ T-cell precursors display structured TCR repertoires and composite antigen-driven selection dynamics

Immunol Cell Biol. 2015 Aug;93(7):625-33. doi: 10.1038/icb.2015.17. Epub 2015 Mar 24.


Basic parameters of the naive antigen (Ag)-specific T-cell repertoire in humans remain poorly defined. Systematic characterization of this 'ground state' immunity in comparison with memory will allow a better understanding of clonal selection during immune challenge. Here, we used high-definition cell isolation from umbilical cord blood samples to establish the baseline frequency, phenotype and T-cell antigen receptor (TCR) repertoire of CD8(+) T-cell precursor populations specific for a range of viral and self-derived Ags. Across the board, these precursor populations were phenotypically naive and occurred with hierarchical frequencies clustered by Ag specificity. The corresponding patterns of TCR architecture were highly ordered and displayed partial overlap with adult memory, indicating biased structuring of the T-cell repertoire during Ag-driven selection. Collectively, these results provide new insights into the complex nature and dynamics of the naive T-cell compartment.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging / immunology
  • Autoantigens / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Clonal Selection, Antigen-Mediated*
  • Dasatinib / pharmacology
  • Fetal Blood / cytology
  • Fetal Blood / immunology*
  • Flow Cytometry
  • HLA Antigens / immunology
  • Hematopoietic Stem Cells / immunology*
  • Humans
  • Immunologic Memory
  • Immunomagnetic Separation
  • Immunophenotyping
  • Infant, Newborn
  • Peptide Fragments / immunology
  • Phosphoproteins / immunology*
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • T-Cell Antigen Receptor Specificity*
  • Viral Matrix Proteins / immunology*


  • Autoantigens
  • HLA Antigens
  • Peptide Fragments
  • Phosphoproteins
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa
  • Dasatinib