Abstract
Abstract In human adults, the majority of peripheral blood gd T cells expresses T cell receptors (TCR) using the Vg9 and Vd2 chains and recognize small nonpeptidic phosphorylated antigens. In contrast, most tissue-derived gd T cells, which are located mainly in spleen and epithelia, preferentially use Vd1 or Vd3 chains paired with diverse Vg chains to form their TCR. Our knowledge about the antigenic specificity and costimulation requirements of human Vd2neg gd T cells remains limited. To address this, we characterized the specificity of a murine mAb (#256), screened for its ability to specifically inhibit cytolytic responses of several human Vd2neg gd T cell clones (such as the Vg8Vd3 T cell clone #73R9) against transformed B cells (e.g. B-LCLs and Burkitt’s lymphomas). Using gd#73R9-derived TCR transfectants and comparative gene expression arrays, we show that mAb#256 does not target a gdTCR ligand, but blocks a key activation pathway involving interaction between non-TCR molecules on effector gd T cells and ILT2 (LILRB1/CD85j) molecule, expressed by tumor targets. In line with the previously reported specificity of this NK receptor for classical and non-classical MHC-I molecules, blockade of MHCgd class I / ILT2 interactions using MHC I- or ILT2-specific mAbs and ILT2-Fc molecules, gdinhibited tumor-induced activation of Vg8Vd3 T cell clones. Therefore, this study describes a new CTL activation pathway involving MHC class I engagement on gd T cells.
Published Version
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