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The Journal of Immunology, 2001, 167: 6239-6246.
Copyright © 2001 by The American Association of Immunologists

TCR{beta} Chain Influences But Does Not Solely Control Autoreactivity of V{alpha}14J281T Cells1

Ming Gui, Jin Li, Li-Jun Wen, Richard R. Hardy and Kyoko Hayakawa2

Fox Chase Cancer Center, Philadelphia, PA 19111

CD1d-dependent accumulation of {alpha}{beta} 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 V{alpha}14+ 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 V{alpha}14 {alpha}-chain plays a primary role, necessary but not sufficient for imparting {alpha}-GalCer/CD1d recognition. {beta}-Chain usage alone is not the sole factor that controls the extent of autoreactivity in V{alpha}14+ T cells, since transduction of TCR{alpha}{beta} chains from a high CD1d autoreactive V{alpha}14+ T cell line conferred the {alpha}-GalCer/CD1d specificity without induction of autoreactivity. Thus, heterogeneity of V{alpha}14+ T cell reactivity is due to both {beta}-chain diversity and control mechanism(s) beyond primary TCR structure.




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