title: Self epitopes shared between human skeletal myosin and Streptococcus pyogenes M5 protein are targets of immune responses in active juvenile dermatomyositis.
abstract: OBJECTIVE
  To identify self T cell epitopes associated with proinflammatory immune responses and clinically active juvenile dermatomyositis (juvenile DM). The target of our search for relevant epitopes was represented by amino acid sequences shared between human skeletal myosin and Streptococcus pyogenes M5 protein. The long-term objective of the project is to identify suitable targets for immunotherapy of the disease.
  
  
  METHODS
  We used computerized algorithms to identify putative agretopes on both the human myosin and Streptococcus M5 proteins. Direct binding assays for homolog peptides were used to confirm such predictions. Antigenicity and functional cross-reactivity were evaluated by cytotoxicity assays and by measurement of cytokine levels. Specific T cells were isolated by T cell capture, and T cell receptor (TCR) V(beta) gene usage was identified by reverse transcriptase-polymerase chain reaction.
  
  
  RESULTS
  We identified peptides that are targets of disease-specific cytotoxic T cell responses. T cell reactivity against the self peptides correlates with clinical signs of early, active myositis. Such reactivity is accompanied by production of proinflammatory cytokines, which may contribute to the damage. T cell cross-recognition of bacterial and human homologs was shown functionally as well as by sorting peptide-specific T cells and identifying oligoclonal and largely overlapping TCR V(beta) gene usage.
  
  
  CONCLUSIONS
  These findings represent the first identification of a self epitope in juvenile DM, providing a potential candidate for antigen-specific immune therapy.
authors.affiliation: IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Massa
authors.forename: Nick
authors.initials: N
authors.lastname: Costouros
authors.forename: Federica
authors.initials: F
authors.lastname: Mazzoli
authors.forename: Fabrizio
authors.initials: F
authors.lastname: De Benedetti
authors.forename: Antonio
authors.initials: A
authors.lastname: La Cava
authors.forename: Tho
authors.initials: T
authors.lastname: Le
authors.forename: Isme
authors.initials: I
authors.lastname: De Kleer
authors.forename: Angelo
authors.initials: A
authors.lastname: Ravelli
authors.forename: Margaret
authors.initials: M
authors.lastname: Liotta
authors.forename: Sarah
authors.initials: S
authors.lastname: Roord
authors.forename: Charles
authors.initials: C
authors.lastname: Berry
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Pachman
authors.forename: Alberto
authors.initials: A
authors.lastname: Martini
authors.forename: Salvatore
authors.initials: S
authors.lastname: Albani
mesh_terms: D001426:Bacterial Proteins / Q000276:immunology*; D002648:Child; D003429:Cross Reactions; D003882:Dermatomyositis / Q000276:immunology* / Q000628:therapy; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D009218:Myosins / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic
chemical_list: D001426:Bacterial Proteins; D000939:Epitopes; D009218:Myosins