T follicular helper and T follicular regulatory cells have different TCR specificity

Nat Commun. 2017 Apr 21;8:15067. doi: 10.1038/ncomms15067.


Immunization leads to the formation of germinal centres (GCs) that contain both T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Whether T-cell receptor (TCR) specificity defines the differential functions of Tfh and Tfr cells is unclear. Here we show that antigen-specific T cells after immunization are preferentially recruited to the GC to become Tfh cells, but not Tfr cells. Tfh cells, but not Tfr cells, also proliferate efficiently on restimulation with the same immunizing antigen in vitro. Ex vivo TCR repertoire analysis shows that immunization induces oligoclonal expansion of Tfh cells. By contrast, the Tfr pool has a TCR repertoire that more closely resembles that of regulatory T (Treg) cells. Our data thus indicate that the GC Tfh and Tfr pools are generated from distinct TCR repertoires, with Tfh cells expressing antigen-responsive TCRs to promote antibody responses, and Tfr cells expressing potentially autoreactive TCRs to suppress autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / administration & dosage
  • Amino Acid Sequence
  • Animals
  • Antigens / administration & dosage
  • Antigens, Bacterial / administration & dosage
  • Autoimmunity
  • Bacterial Proteins / administration & dosage
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / immunology
  • Cell Proliferation / drug effects
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Female
  • Gene Expression Regulation
  • Germinal Center / cytology
  • Germinal Center / drug effects
  • Germinal Center / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Ovalbumin / administration & dosage
  • Receptors, Antigen, T-Cell / classification
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*


  • Antigens
  • Antigens, Bacterial
  • Bacterial Proteins
  • Receptors, Antigen, T-Cell
  • Ovalbumin
  • Acyltransferases
  • antigen 85B, Mycobacterium tuberculosis