TCRβ Chain Influences But Does Not Solely Control Autoreactivity of Vα14J281T Cells

Abstract

CD1d-dependent accumulation of αβ T cells bearing a canonical Vα14Jα281 α-chain (Vα14+ 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 Vα14+ T cells do not exhibit significant autoreactivity despite high reactivity to α-galactosylceramide presented by CD1d (α-GalCer/CD1d). To assess the role of TCRβ chain in determining the α-GalCer/CD1d vs autoreactive specificity of Vα14+ T cells, we conducted TCRα or TCRβ chain transduction experiments. In this study we demonstrate, by combining different TCRβ chains with the Vα14 α-chain in retrovirally transduced T cell lines, that the Vα14 α-chain plays a primary role, necessary but not sufficient for imparting α-GalCer/CD1d recognition. β-Chain usage alone is not the sole factor that controls the extent of autoreactivity in Vα14+ T cells, since transduction of TCRαβ chains from a high CD1d autoreactive Vα14+ T cell line conferred the α-GalCer/CD1d specificity without induction of autoreactivity. Thus, heterogeneity of Vα14+ T cell reactivity is due to both β-chain diversity and control mechanism(s) beyond primary TCR structure.