A viral peptide with limited homology to a self peptide can induce clinical signs of experimental autoimmune encephalomyelitis.
Molecular mimicry has been suggested as a mode of autoreactive T cell stimulation in autoimmune diseases. Myelin basic protein (MBP) peptide 1-11 induces experimental autoimmune encephalomyelitis (EAE) in susceptible strains of mice. Here we show that a herpesvirus Saimiri (HVS) peptide, AAQRRPSRPFA, with a limited homology to MBP1-11 peptide, ASQKRPSQRHG (underlined letters showing homology), can stimulate a panel of MBP-11-specific T cell hybridomas and more importantly cause EAE in mice. We demonstrate that this is due to cross-recognition of these two peptides by TCRs. Results presented in this communication are the first demonstration that a viral peptide with homology at just 5 amino acids with a self peptide can induce clinical signs of EAE in mice. These findings have important implications in understanding the breakdown of T cell tolerance to self Ags in autoimmune diseases by means of cross-reactivity with unrelated peptides.
Gautam
A M
AM
Division of Immunology and Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra. AG@ME.DK
Liblau
R
R
Chelvanayagam
G
G
Steinman
L
L
Boston
T
T
D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D003429:Cross Reactions; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D006567:Herpesvirus 2, Saimiriine / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006825:Hybridomas / Q000276:immunology; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology
D000956:Antigens, Viral; D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010446:Peptide Fragments