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  • Title: Species-specific immune responses generated by histidyl-tRNA synthetase immunization are associated with muscle and lung inflammation.
    Author: Katsumata Y, Ridgway WM, Oriss T, Gu X, Chin D, Wu Y, Fertig N, Oury T, Vandersteen D, Clemens P, Camacho CJ, Weinberg A, Ascherman DP.
    Journal: J Autoimmun; 2007; 29(2-3):174-86. PubMed ID: 17826948.
    Abstract:
    Evidence implicating histidyl-tRNA synthetase (Jo-1) in the pathogenesis of the anti-synthetase syndrome includes established genetic associations linking the reproducible phenotype of muscle inflammation and interstitial lung disease with autoantibodies recognizing Jo-1. To better address the role of Jo-1-directed B and T cell responses in the context of different genetic backgrounds, we employed Jo-1 protein immunization of C57BL/6 and NOD congenic mice. Detailed analysis of early antibody responses following inoculation with human or murine Jo-1 demonstrates remarkable species-specifity, with limited cross recognition of Jo-1 from the opposite species. Complementing these results, immunization with purified peptides derived from murine Jo-1 generates B and T cells targeting species-specific epitopes contained within the amino terminal 120 amino acids of murine Jo-1. The eventual spreading of B cell epitopes that uniformly occurs 8 weeks post immunization with murine Jo-1 provides additional evidence of an immune response mediated by autoreactive, Jo-1-specific T cells. Corresponding to this self-reactivity, mice immunized with murine Jo-1 develop a striking combination of muscle and lung inflammation that replicates features of the human anti-synthetase syndrome.
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