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.
Original language | English (US) |
---|---|
Pages (from-to) | 174-186 |
Number of pages | 13 |
Journal | Journal of Autoimmunity |
Volume | 29 |
Issue number | 2-3 |
DOIs | |
State | Published - Sep 2007 |
Keywords
- Animal models
- Autoantibodies
- Autoantigens
- Inflammatory myopathy
- Lung inflammation
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy