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

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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

Cite this

Thoua, N. M., van Noort, J. M., Baker, D., Bose, A., van Sechel, A. C., van Stipdonk, M. J., ... Amor, S. (2000). Encephalitogenic and immunogenic potential of the stress protein alphaB-crystallin in Biozzi ABH (H-2A(g7)) mice. Journal of Neuroimmunology, 104(1), 47-57.