NKT Cell-TCR Expression Activates Conventional T Cells in Vivo,but Is Largely Dispensable for Mature NKT Cell Biology |
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| Authors: | J Christoph Vahl Klaus Heger Nathalie Knies Marco Y Hein Louis Boon Hideo Yagita Bojan Polic Marc Schmidt-Supprian |
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| Institution: | 1.Molecular Immunology and Signaltransduction, Max Planck Institute of Biochemistry, Martinsried, Germany;2.Bioceros, Yalelaan 46, Utrecht, The Netherlands;3.Juntendo University School of Medicine, Tokyo, Japan;4.University of Rijeka School of Medicine, Rijeka, Croatia;National Jewish Medical and Research Center/Howard Hughes Medical Institute, United States of America |
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| Abstract: | Natural killer T (NKT) cell development depends on recognition of self-glycolipids via their semi-invariant Vα14i-TCR. However, to what extent TCR-mediated signals determine identity and function of mature NKT cells remains incompletely understood. To address this issue, we developed a mouse strain allowing conditional Vα14i-TCR expression from within the endogenous Tcrα locus. We demonstrate that naïve T cells are activated upon replacement of their endogenous TCR repertoire with Vα14i-restricted TCRs, but they do not differentiate into NKT cells. On the other hand, induced TCR ablation on mature NKT cells did not affect their lineage identity, homeostasis, or innate rapid cytokine secretion abilities. We therefore propose that peripheral NKT cells become unresponsive to and thus are independent of their autoreactive TCR. |
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