Cutting edge:: Influence of the TCR Vβ domain on the selection of semi-invariant NKT cells by endogenous ligands

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 V beta 8.2 and V beta 7. Whereas the TCR V beta domain influences the binding avidity of the V alpha 14i TCR for CD1d-alpha-galactosylceramide complexes, with V beta 8.2 conferring higher avidity binding than V beta 7, apossihle impact of the TCR V beta domain on V alpha 14i NKT cell selection by endogenous ligands has not been studied. In this study, we show that thymic selection of V beta(7+), but not V beta 8.2(+), V alpha 14i NKT cells isfavored in situations where endogenous ligand concentration or TCR alpha-chain avidity are suboptimal. Furthermore, thymic V beta 7(+) V alpha 14i NKT celb were preferentially selected in vitro in response to CD1d-dependent presentation of endogenous ligands or exogenously added self ligand isoglobotribexosylceramide. Collectively, our data demonstrate that the TCR V beta domain influences the selection of V alpha 14i NKT cells 4 endogenous ligands, presumably because V beta 7 confers higher avidity binding.