T cell immunity. Functional heterogeneity of human memory CD4⁺ T cell clones primed by pathogens or vaccines

Science. 2015 Jan 23;347(6220):400-6. doi: 10.1126/science.1260668. Epub 2014 Dec 4.


Distinct types of CD4(+) T cells protect the host against different classes of pathogens. However, it is unclear whether a given pathogen induces a single type of polarized T cell. By combining antigenic stimulation and T cell receptor deep sequencing, we found that human pathogen- and vaccine-specific T helper 1 (T(H)1), T(H)2, and T(H)17 memory cells have different frequencies but comparable diversity and comprise not only clones polarized toward a single fate, but also clones whose progeny have acquired multiple fates. Single naïve T cells primed by a pathogen in vitro could also give rise to multiple fates. Our results unravel an unexpected degree of interclonal and intraclonal functional heterogeneity of the human T cell response and suggest that polarized responses result from preferential expansion rather than priming.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • CD4-Positive T-Lymphocytes / immunology*
  • Candida albicans / immunology*
  • Cells, Cultured
  • Clone Cells
  • High-Throughput Nucleotide Sequencing
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Immunologic Memory*
  • Lymphocyte Activation
  • Molecular Sequence Data
  • Mycobacterium tuberculosis / immunology*
  • Receptors, Antigen, T-Cell / genetics
  • T-Lymphocyte Subsets / immunology*
  • Th1 Cells / immunology
  • Th17 Cells / immunology
  • Th2 Cells / immunology
  • Vaccines / immunology*


  • Receptors, Antigen, T-Cell
  • Vaccines