Encephalitogenic and immunogenic potential of the stress protein alphaB-crystallin in Biozzi ABH (H-2A(g7)) mice.
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.
Thoua
N M
NM
Department of Immunology, Rayne Institute, United Medical and Dental Schools of Guy's and St Thomas', London, UK.
van Noort
J M
JM
Baker
D
D
Bose
A
A
van Sechel
A C
AC
van Stipdonk
M J
MJ
Travers
P J
PJ
Amor
S
S
D000818:Animals; D002417:Cattle; D003459:Crystallins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D004660:Encephalitis / Q000276:immunology*; D000939:Epitopes; D008221:Lymphoid Tissue / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains / Q000502:physiology*; D008956:Models, Chemical; D008968:Molecular Conformation; D010449:Peptide Mapping; D013601:T-Lymphocytes / Q000276:immunology
D003459:Crystallins; D000939:Epitopes