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 |
|---|---|
| Pages (from-to) | 174-186 |
| Number of pages | 13 |
| Journal | Journal of Autoimmunity |
| Volume | 29 |
| Issue number | 2-3 |
| DOIs | |
| State | Published - Sep 1 2007 |
| Externally published | Yes |
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Keywords
- Animal models
- Autoantibodies
- Autoantigens
- Inflammatory myopathy
- Lung inflammation
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Species-specific immune responses generated by histidyl-tRNA synthetase immunization are associated with muscle and lung inflammation. / Katsumata, Yasuhiro; Ridgway, William M.; Oriss, Timothy; Gu, Xinyan; Chin, David; Wu, Yuehong; Fertig, Noreen; Oury, Tim; Vandersteen, Daniel; Clemens, Paula; Camacho, Carlos J.; Weinberg, Andrew; Ascherman, Dana.
In: Journal of Autoimmunity, Vol. 29, No. 2-3, 01.09.2007, p. 174-186.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Species-specific immune responses generated by histidyl-tRNA synthetase immunization are associated with muscle and lung inflammation
AU - Katsumata, Yasuhiro
AU - Ridgway, William M.
AU - Oriss, Timothy
AU - Gu, Xinyan
AU - Chin, David
AU - Wu, Yuehong
AU - Fertig, Noreen
AU - Oury, Tim
AU - Vandersteen, Daniel
AU - Clemens, Paula
AU - Camacho, Carlos J.
AU - Weinberg, Andrew
AU - Ascherman, Dana
PY - 2007/9/1
Y1 - 2007/9/1
N2 - 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.
AB - 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.
KW - Animal models
KW - Autoantibodies
KW - Autoantigens
KW - Inflammatory myopathy
KW - Lung inflammation
UR - http://www.scopus.com/inward/record.url?scp=34548594045&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548594045&partnerID=8YFLogxK
U2 - 10.1016/j.jaut.2007.07.005
DO - 10.1016/j.jaut.2007.07.005
M3 - Article
VL - 29
SP - 174
EP - 186
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
SN - 0896-8411
IS - 2-3
ER -