Induction of experimental autoimmune encephalomyelitis by pathogen derived peptides

R. Ufret-Vincenty, S. H. Pak, L. Quigley, K. Wucherfennig, S. Brocke

Research output: Contribution to journalArticle

Abstract

Although a large body of circumstantial evidence supports the existence of crossreacting antigens between microorganisms and host, the relevance of this phenomenom as a causal factor in the development of autoimmune disease remains unclear. Experimental Autoimmune Encephalomyelitis (EAE) induced by myelin basic protein peptide (87-99) in mice is an excellent experimental system to address this issue. We screened a large number of peptides derived from different infectious agents. The peptides were chosen for their structural homology to MBP(87-99) using a computer search in which conservative substitutions were allowed. We identified three viral peptides that show a significant degree of crossreactivity in vitro with MBP(87-99), even when their sequence homology to this autoantigen is low. Repeated stimulation of T cells specific for a peptide from Human Papilloma Virus using the same viral peptide, even in very low doses, selects a population of cross reactive and potently encephalitogenic cells. Furthermore, these viral peptide-specific cells that had not been exposed to the autoantigen could be activated by a second unrelated peptide (from EBV) also leading to autoimmune disease. These results provide evidence for a causal role of crossreactivity at the level of the T cell receptor in organ-specific autoimmunity. They also suggest that multiple antigenic stimulations, either with the same or different pathogen-derived peptides, might be necessary for the induction of autoimmune disease.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

Fingerprint

Autoimmune Experimental Encephalomyelitis
Pathogens
encephalitis
peptides
Peptides
pathogens
autoimmune diseases
Autoimmune Diseases
autoantigens
Papillomaviridae
T-lymphocytes
T-cells
papilloma
autoimmunity
Sequence Homology
T-Cell Antigen Receptor
Autoimmunity
Human Herpesvirus 4
Viruses
Microorganisms

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Ufret-Vincenty, R., Pak, S. H., Quigley, L., Wucherfennig, K., & Brocke, S. (1998). Induction of experimental autoimmune encephalomyelitis by pathogen derived peptides. FASEB Journal, 12(5).

Induction of experimental autoimmune encephalomyelitis by pathogen derived peptides. / Ufret-Vincenty, R.; Pak, S. H.; Quigley, L.; Wucherfennig, K.; Brocke, S.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

Ufret-Vincenty, R, Pak, SH, Quigley, L, Wucherfennig, K & Brocke, S 1998, 'Induction of experimental autoimmune encephalomyelitis by pathogen derived peptides', FASEB Journal, vol. 12, no. 5.
Ufret-Vincenty, R. ; Pak, S. H. ; Quigley, L. ; Wucherfennig, K. ; Brocke, S. / Induction of experimental autoimmune encephalomyelitis by pathogen derived peptides. In: FASEB Journal. 1998 ; Vol. 12, No. 5.
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