title: Autoantigen cross-reactive environmental antigen can trigger multiple sclerosis-like disease.
abstract: BACKGROUND
  Multiple sclerosis is generally considered an autoimmune disease resulting from interaction between predisposing genes and environmental factors, together allowing immunological self-tolerance to be compromised. The precise nature of the environmental inputs has been elusive, infectious agents having received considerable attention. A recent study generated an algorithm predicting naturally occurring T cell receptor (TCR) ligands from the proteome database. Taking the example of a multiple sclerosis patient-derived anti-myelin TCR, the study identified a number of stimulatory, cross-reactive peptide sequences from environmental and human antigens. Having previously generated a spontaneous multiple sclerosis (MS) model through expression of this TCR, we asked whether any of these could indeed function in vivo to trigger CNS disease by cross-reactive activation.
  
  
  RESULTS
  A number of myelin epitope cross-reactive epitopes could stimulate T cell immunity in this MS anti-myelin TCR transgenic model. Two of the most stimulatory of these 'environmental' epitopes, from Dictyostyelium slime mold and from Emiliania huxleyi, were tested for the ability to induce MS-like disease in the transgenics. We found that immunization with cross-reactive peptide from Dictyostyelium slime mold (but not from E. huxleyi) induces severe disease.
  
  
  CONCLUSIONS
  These specific environmental epitopes are unlikely to be common triggers of MS, but this study suggests that our search for the cross-reactivity triggers of autoimmune activation leading to MS should encompass epitopes not just from the 'infectome' but also from the full environmental 'exposome.'
authors.affiliation: Lung Immunology Group, Section of Infectious Diseases and Immunity, Division of Infectious Diseases, Department of Medicine, Hammersmith Hospital, Imperial College London, Room 8N22, Commonwealth Building, Du Cane Road, London, W12 ONN, UK. c.reynolds@imperial.ac.uk.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Reynolds
authors.affiliation: Lung Immunology Group, Section of Infectious Diseases and Immunity, Division of Infectious Diseases, Department of Medicine, Hammersmith Hospital, Imperial College London, Room 8N22, Commonwealth Building, Du Cane Road, London, W12 ONN, UK. malcolm.sim06@imperial.ac.uk.
authors.forename: Malcolm J W
authors.initials: MJ
authors.lastname: Sim
authors.affiliation: Lung Immunology Group, Section of Infectious Diseases and Immunity, Division of Infectious Diseases, Department of Medicine, Hammersmith Hospital, Imperial College London, Room 8N22, Commonwealth Building, Du Cane Road, London, W12 ONN, UK. kathryn.quigley09@imperial.ac.uk.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Quigley
authors.affiliation: Section of Molecular Immunology, Division of Immunology and Inflammation, Department of Medicine, Hammersmith Hospital, Imperial College London, Du Cane Road, London, W12 ONN, UK. d.altmann@imperial.ac.uk.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Altmann
authors.affiliation: Lung Immunology Group, Section of Infectious Diseases and Immunity, Division of Infectious Diseases, Department of Medicine, Hammersmith Hospital, Imperial College London, Room 8N22, Commonwealth Building, Du Cane Road, London, W12 ONN, UK. r.boyton@imperial.ac.uk.
authors.forename: Rosemary J
authors.initials: RJ
authors.lastname: Boyton
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001424:Bacterial Infections / Q000276:immunology; D004195:Disease Models, Animal; D004783:Environmental Microbiology; D059810:HLA-DR Serological Subtypes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D004676:Myelin Basic Protein / Q000378:metabolism; D037342:Pertussis Toxin / Q000633:toxicity; D011528:Protozoan Infections / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001324:Autoantigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D037342:Pertussis Toxin