T follicular helper (Tfh) cells are fundamental for B cell selection and antibody maturation in germinal centers. Circulating Tfh (cTfh) cells constitute a minor proportion of the CD4+ T cells in peripheral blood, but their clonotypic relationship to Tfh populations resident in lymph nodes and the extent to which they differ from non-Tfh CD4+ cells have been unclear. Using donor-matched blood and tonsil samples, we investigate T cell receptor (TCR) sharing between tonsillar Tfh cells and peripheral Tfh and non-Tfh cell populations. TCR transcript sequencing reveals considerable clonal overlap between peripheral and tonsillar Tfh cell subsets as well as a clear distinction between Tfh and non-Tfh cells. Furthermore, influenza-specific cTfh cell clones derived from blood can be found in the repertoire of tonsillar Tfh cells. Therefore, human blood samples can be used to gain insight into the specificity of Tfh responses occurring in lymphoid tissues, provided that cTfh subsets are studied.

Central European Institute of Technology Brno 601 77 Czech Republic

Central European Institute of Technology Brno 601 77 Czech Republic; Center for Precision Genome Editing and Genetic Technologies for Biomedicine Pirogov Russian National Research Medical University Moscow 117997 Russia; Shemyakin Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Science Moscow 117997 Russia

Division of Infection and Immunity Cardiff University School of Medicine Cardiff CF14 4XN UK

Division of Infection and Immunity Cardiff University School of Medicine Cardiff CF14 4XN UK; Systems Immunity Research Institute Cardiff University School of Medicine Cardiff CF14 4XN UK

Istituto Firc di Oncologia Molecolare Milano 20139 Italy

Nuffield Department of Clinical Medicine University of Oxford Oxford OX3 7FZ UK

The Jenner Institute University of Oxford Oxford OX3 7DQ UK

West Wing ENT John Radcliffe Hospital Oxford OX3 9DU UK

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