Target Specificity of an Autoreactive Pathogenic Human γδ-T Cell Receptor in Myositis

• DOI: 10.1074/jbc.m112.356709
• Publication Date: 2012-05-02T00:18:10Z
• Authors: Jessica Bruder; Katherina Siewert; Birgit Obermeier; Joachim Malotka; Peter Scheinert; Josef Kellermann; Takuya Ueda; Reinhard Hohlfeld; Klaus Dornmair
• Keywords: Inclusion body myositis

In polymyositis and inclusion body myositis, muscle fibers are surrounded invaded by CD8-positive cytotoxic T cells expressing the αβ-T cell receptor (αβ-TCR) for antigen. a rare variant of similarly attacked CD8-negative γδ-TCR (γδ-T cell-mediated myositis). We investigated antigen specificity human previously identified in an autoimmune tissue lesion γδ-T myositis. show that this Vγ1.3Vδ2-TCR, termed M88, recognizes various proteins from different species. Several these belong to translational apparatus, including some bacterial aminoacyl-tRNA synthetases (AA-RS). Specifically, M88 histidyl-tRNA synthetase, known be also targeted autoantibodies called anti-Jo-1. The target epitope is strictly conformational, independent post-translational modification, exposed on surface respective antigenic protein. Extensive mutagenesis translation initiation factor-1 Escherichia coli (EcIF1), which served as paradigm with structure, showed short α-helical loop around amino acids 39 42 EcIF1 major part epitope. Mutagenesis complementarity determining regions 3 both chains contribute recognition. only example molecularly characterized expressed autoaggressive tissue. observation AA-RS reveals unexpected link between antibody responses