Encephalitogenic and immunogenic potential of the stress protein alphaB-crystallin in Biozzi ABH (H-2A(g7)) mice

N M Thoua, J M van Noort, D Baker, A Bose, A C van Sechel, M J van Stipdonk, P J Travers, S Amor

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The stress protein alphaB-crystallin is an immunodominant antigen in multiple sclerosis (MS)-affected myelin for human T cells and is expressed at elevated levels in MS lesions. Using bovine alphaB-crystallin and synthetic peptides based on mouse alphaB-crystallin the ability of this stress protein to induce experimental allergic encephalomyelitis (EAE) was screened in Biozzi ABH (H-2A(g7)) mice. While whole alphaB-crystallin and the immunodominant T cell epitopes (49-64, 73-88, 153-168) failed to induce disease the subdominant or cryptic epitope (1-16) was weakly encephalitogenic. The lack of encephalitogenicity of whole protein and dominant epitopes may be due to the low constitutive expression of alphaB-crystallin in the CNS combined with a state of peripheral tolerance suggested by the constitutive expression of alphaB-crystallin in secondary lymphoid tissues in ABH mice. Further evidence for a role of alphaB-crystallin in the progression of chronic relapsing neurological disease is suggested by the development of T cell responses to alphaB-crystallin during MOG-induced relapsing EAE as myelin damage accumulates. Together our data indicate that normal tolerising mechanisms in ABH mice prevent the induction of EAE by alphaB-crystallin while the subdominant or cryptic epitope is able to circumvent these mechanisms and contribute to pathogenic myelin-directed autoimmunity following T cell activation.

Original languageEnglish
Pages (from-to)47-57
Number of pages11
JournalJournal of Neuroimmunology
Volume104
Issue number1
Publication statusPublished - 3 Apr 2000

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