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The Journal of Immunology, 2006, 176: 2064-2068.
Copyright © 2006 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Influence of the TCR Vbeta Domain on the Selection of Semi-Invariant NKT Cells by Endogenous Ligands1

Jens Schümann2,*, Marcin P. Mycko*, Paolo Dellabona{dagger}, Giulia Casorati{dagger} and H. Robson MacDonald3,*

* Ludwig Institute for Cancer Research, Epalinges, Switzerland; and {dagger} Department of Biology and Technology, H. San Raffaele Scientific Institute, Milan, Italy

Invariant V{alpha}14 (V{alpha}14i) NKT cells are a murine CD1d-dependent regulatory T cell subset characterized by a V{alpha}14-J{alpha}18 rearrangement and expression of mostly Vbeta8.2 and Vbeta7. Whereas the TCR Vbeta domain influences the binding avidity of the V{alpha}14i TCR for CD1d-{alpha}-galactosylceramide complexes, with Vbeta8.2 conferring higher avidity binding than Vbeta7, a possible impact of the TCR Vbeta domain on V{alpha}14i NKT cell selection by endogenous ligands has not been studied. In this study, we show that thymic selection of Vbeta7+, but not Vbeta8.2+, V{alpha}14i NKT cells is favored in situations where endogenous ligand concentration or TCR{alpha}-chain avidity are suboptimal. Furthermore, thymic Vbeta7+ V{alpha}14i 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 Vbeta domain influences the selection of V{alpha}14i NKT cells by endogenous ligands, presumably because Vbeta7 confers higher avidity binding.




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