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.
- Patricia Barral
- Rebeca Jimeno
- Graham Anderson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All animal experiments were approved by the Francis Crick Institute's and the King's College London's Animal Welfare and Ethical Review Body and the United Kingdom Home Office.
Human subjects: Human tissues used in this study were collected with ethical approval from UK Research Ethics Committees administered through the Integrated Research Application System. All samples were collected with informed consent.
- Chyung-Ru Wang, Northwestern University, United States
© 2019, Jimeno et al.
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