Involvement of epitope mimicry in potentiation but not initiation of autoimmune disease.
We have examined whether the peptide (368-381) from the murine adenovirus type 1 E1B sequence, exhibiting a high degree of homology with the known pathogenic thyroglobulin (Tg) T cell epitope (2695-2706), can induce experimental autoimmune thyroiditis (EAT) in SJL/J mice. The viral peptide was a poor immunogen at the T or B cell level and did not elicit EAT either directly or by adoptive transfer assays. Surprisingly, however, the viral peptide was highly antigenic in vitro, activating a Tg2695-2706-specific T cell clone and reacting with serum IgG from mice primed with the Tg homologue. The viral peptide also induced strong recall responses in Tg2695-2706-primed lymph node cells, and subsequent adoptive transfer of these cells into naive mice led to development of highly significant EAT. These data demonstrate that nonimmunogenic viral peptides can act as agonists for preactivated autoreactive T cells and suggest that epitope mimicry may at times play a potentiating rather than a precipitating role in the pathogenesis of autoimmune disease.
Rao
V P
VP
Department of Genetics, University of Georgia, Athens, GA 30602; and Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
Kajon
A E
AE
Spindler
K R
KR
Carayanniotis
G
G
D017501:Adenovirus E1B Proteins / Q000276:immunology*; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D000939:Epitopes; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D018716:Molecular Mimicry; D010446:Peptide Fragments / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology; D013954:Thyroglobulin / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000209:etiology / Q000276:immunology*
D017501:Adenovirus E1B Proteins; D001324:Autoantigens; D000939:Epitopes; D007376:Interleukin-2; D010446:Peptide Fragments; C119311:adenovirus E1B protein (368-381); C119310:thyroglobulin peptide (2695-2706); D013954:Thyroglobulin