TCRβ chain influences but does not solely control autoreactivity of Vα14J281T cells

CD1d-dependent accumulation of ap T cells bearing a canonical V alpha 14J alpha 281 alpha -chain (V alpha 14(+) T cells) is thought to model positive selection of lipid-specific T cells, based on their ability to recognize CD1d-presented self glycolipid(s). However, it has been difficult to demonstrate self ligand specificity in this system, as most Va14(+) T cells do not exhibit significant autoreactivity despite high reactivity to alpha -galactosylceramide presented by CD1d (alpha -GalCer/CD1d). To assess the role of TCR beta chain in determining the alpha -GalCer/CD1d vs autoreactive specificity of V alpha 14(+) T cells, we conducted TCR alpha or TCR beta chain transduction experiments. In this study we demonstrate, by combining different TCR beta chains with the V alpha 14 alpha -chain in retrovirally transduced T cell lines, that the Va14 alpha -chain plays a primary role, necessary but not sufficient for imparting a-GalCer/CD1d recognition. beta -Chain usage alone is not the sole factor that controls the extent of autoreactivity in Va14(+) T cells, since transduction of TCR alpha beta chains from a high CD1d autoreactive Va14(+) T cell line conferred the alpha -GalCer/CD1d specificity without induction of autoreactivity. Thus, heterogeneity of Va14(+) T cell reactivity is due to both beta -chain diversity and control mechanism(s) beyond primary TCR structure.