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

Abstract

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