Proteolytic cleavage of a self-antigen following xenobiotic-induced cell death produces a fragment with novel immunogenic properties

Citation
Km. Pollard et al., Proteolytic cleavage of a self-antigen following xenobiotic-induced cell death produces a fragment with novel immunogenic properties, J IMMUNOL, 165(4), 2000, pp. 2263-2270
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
0022-1767 → ACNP
Volume
165
Issue
4
Year of publication
2000
Pages
2263 - 2270
Database
ISI
SICI code
0022-1767(20000815)165:4<2263:PCOASF>2.0.ZU;2-J
Abstract
The heavy metal mercury elicits a genetically restricted autoantibody respo nse in mice that targets the nucleolar autoantigen fibrillarin, HgCl2-induc ed cell death of macrophages resulted in the proteolytic cleavage of fibril larin, A prominent feature of mercury-induced cell death was the generation of a 19-kDa fragment of fibrillarin that was not found following apoptotic or nonapoptotic cell death induced by stimuli other than mercury. Proteoly sis of fibrillarin lacking cysteines, and therefore unable to bind mercury, also produced the 19-kDa fragment, suggesting that a mercury-fibrillarin i nteraction was not necessary for the unique cleavage pattern of this self-A g. In contrast to immunization with full-length fibrillarin, the 19-kDa fra gment produced anti-fibrillarin Abs with some of the properties of the HgCl 2-induced anti-fibrillarin response. We propose that cell death following e xposure to an autoimmunity-inducing xenobiotic can lead to the generation o f novel protein fragments that may serve as sources of antigenic determinan ts for self-reactive T lymphocytes.