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CUTTING EDGE |
Domain on the Selection of Semi-Invariant NKT Cells by Endogenous Ligands1
* Ludwig Institute for Cancer Research, Epalinges, Switzerland; and
Department of Biology and Technology, H. San Raffaele Scientific Institute, Milan, Italy
Invariant V
14 (V14i) NKT cells are a murine CD1d-dependent regulatory T cell subset characterized by a V14-J18 rearrangement and expression of mostly V
8.2 and V7. Whereas the TCR V domain influences the binding avidity of the V14i TCR for CD1d--galactosylceramide complexes, with V8.2 conferring higher avidity binding than V7, a possible impact of the TCR V domain on V14i NKT cell selection by endogenous ligands has not been studied. In this study, we show that thymic selection of V7+, but not V8.2+, V14i NKT cells is favored in situations where endogenous ligand concentration or TCR-chain avidity are suboptimal. Furthermore, thymic V7+ V14i NKT cells were preferentially selected in vitro in response to CD1d-dependent presentation of endogenous ligands or exogenously added self ligand isoglobotrihexosylceramide. Collectively, our data demonstrate that the TCR V domain influences the selection of V14i NKT cells by endogenous ligands, presumably because V7 confers higher avidity binding.
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