Encephalitogenic and immunogenic potential of the stress protein αB-crystallin in Biozzi ABH (H-2Ag7) mice

The stress protein alpha B-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 alpha B-crystallin and synthetic peptides based on mouse alpha B-crystallin the ability of this stress protein to induce experimental allergic encephalomyelitis (EAE) was screened in Biozzi ABH (H-2A(g7)) mice. While whole alpha B-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 alpha B-crystallin in the CNS combined with a state of peripheral tolerance suggested by the constitutive expression of alpha B-crystallin in secondary lymphoid tissues in ABH mice. Further evidence for a role of alpha B-crystallin in the progression of chronic relapsing neurological disease is suggested by the development of T cell responses to alpha B-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 alpha B-crystallin while the subdominant or cryptic epitope is able to circumvent these mechanisms and contribute to pathogenic myelin-directed autoimmunity following T cell activation. (C) 2000 Elsevier Science B.V. All rights reserved.