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The checkpoint for agonist selection precedes conventional selection in human thymus

par Verstichel, Greet;Vermijlen, David ;Martens, Liesbeth;Goetgeluk, Glenn;Brouwer, Margreet ;Thiault, Nicolas;van Caeneghem, Yasmine;De Munter, Stijn;Weening, Karin;Bonte, Sarah;Leclercq, Georges ;Taghon, Tom;Kerre, Tessa;Saeys, Yvan;Van Dorpe, J.;Cheroutre, Hilde;Vandekerckhove, Bart
Référence Science immunology, 2, page (eaah4232)
Publication Publié, 2017-02-24

Article révisé par les pairs

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Résumé :

The thymus plays a central role in self-tolerance, partly by eliminating precursors with a T cell receptor (TCR) that binds strongly to self-antigens. However, the generation of self-agonist–selected lineages also relies on strong TCR signaling. How thymocytes discriminate between these opposite outcomes remains elusive. Here, we identified a human agonist–selected PD-1+ CD8+ subset of mature CD8+ T cells that displays an effector phenotype associated with agonist selection. TCR stimulation of immature post–-selection thymocyte blasts specifically gives rise to this innate subset and fixes early T cell receptor alpha variable (TRAV) and T cell receptor alpha joining (TRAJ) rearrangements in the TCR repertoire. These findings suggest that the checkpoint for agonist selection precedes conventional selection in the human thymus.