Tissue-specific shaping of the TCR repertoire and antigen specificity of iNKT cells

Research output: Contribution to journalArticle

Authors

  • Rebeca Jimeno
  • Marta Lebrusant-Fernandez
  • Christian Margreitter
  • Gavin Kelly
  • Franca Fraternali
  • Jo Spencer
  • Patricia Barral

Colleges, School and Institutes

External organisations

  • The Francis Crick Institute
  • King's Health Partners Cancer Biobank, King's College London, London, UK.

Abstract

Tissue homeostasis is critically dependent on the function of tissue-resident lymphocytes, including lipid-reactive invariant natural killer T (iNKT) cells. Yet, if and how the tissue environment shapes the antigen specificity of iNKT cells remains unknown. By analysing iNKT cells from lymphoid tissues of mice and humans we demonstrate that their T cell receptor (TCR) repertoire is highly diverse and is distinct for cells from various tissues resulting in differential lipid-antigen recognition. Within peripheral tissues iNKT cell recent thymic emigrants exhibit a different TCR repertoire than mature cells, suggesting that the iNKT population is shaped after arrival to the periphery. Consistent with this, iNKT cells from different organs show distinct basal activation, proliferation and clonal expansion. Moreover, the iNKT cell TCR repertoire changes following immunisation and is shaped by age and environmental changes. Thus, post-thymic modification of the TCR-repertoire underpins the distinct antigen specificity for iNKT cells in peripheral tissues.

Bibliographic note

© 2019, Jimeno et al.

Details

Original languageEnglish
JournalElife
Volume8
Publication statusPublished - 16 Dec 2019

Keywords

  • Animals, Antigens/immunology, Cell Proliferation, Humans, Lipids/immunology, Mice, Natural Killer T-Cells/immunology, Receptors, Antigen, T-Cell/metabolism, Substrate Specificity