title: Potential role of molecular mimicry between human U1-70 kDa and fungal proteins in the development of T-cell mediated anti-U1-70 kDa autoimmunity.
abstract: BACKGROUND
  Molecular mimicry between human and microbial antigens is a possible trigger of autoimmunity. The possible role of this mechanism in the onset of autoimmunity against the human autoantigen U1-70 kDa, typical of mixed connective tissue disease, is not fully elucidated.
  
  
  OBJECTIVE
  We aimed to identify microbial proteins highly similar to U1-70 kDa and potentially triggering anti-U1-70 kDa autoimmunity.
  
  
  METHODS
  We compared in silico the amino acid sequence of human U1-70 kDa and those of all the sequenced fungal, viral and bacterial proteins.
  
  
  RESULTS
  Human U1-70 kDa shares highly significant (E<10(-20)) amino acid sequence homology, spanning a segment containing T-cell epitopes, with 13 fungal (but no viral or bacterial) proteins, belonging to human pathogens. Nine of these proteins include the amino acid sequence VLVDVERGRTV, identical to the most frequent U1-70 kDa T-cell epitope in anti-U1-70 kDa positive patients, and sequences highly similar to the epitope DAFKTLFVARVN (identical residues or conservative residue substitutions in positions crucial for epitope binding).
  
  
  CONCLUSIONS
  Cross-reactivity between human U1-70 kDa and microbial proteins was demonstrated for B-cell epitopes, but never investigated before for T-cell epitopes. Our data identify some fungal proteins as possible triggers of anti-U1-70 kDa autoimmunity via molecular mimicry. Research in this field could improve the understanding of the mechanisms leading to anti-U1-70 kDa autoimmunity, with potential consequences on prevention.
authors.affiliation: Department of Territorial Social Medicine, Section of Dermatology, University of Messina, Messina, Italy. f.guarneri@tiscali.it
authors.forename: F
authors.initials: F
authors.lastname: Guarneri
authors.forename: B
authors.initials: B
authors.lastname: Guarneri
authors.forename: F
authors.initials: F
authors.lastname: Borgia
authors.forename: C
authors.initials: C
authors.lastname: Guarneri
mesh_terms: D001324:Autoantigens / Q000235:genetics* / Q000276:immunology; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D005656:Fungal Proteins / Q000235:genetics* / Q000276:immunology; D005658:Fungi; D006801:Humans; D018716:Molecular Mimicry / Q000235:genetics* / Q000276:immunology; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000235:genetics* / Q000276:immunology; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein
chemical_list: D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D005656:Fungal Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; C490688:SNRNP70 protein, human