Self epitopes shared between human skeletal myosin and Streptococcus pyogenes M5 protein are targets of immune responses in active juvenile dermatomyositis

Margherita Massa, Nick Costouros, Federica Mazzoli, Fabrizio De Benedetti, Antonio La Cava, Tho Le, Isme De Kleer, Angelo Ravelli, Margaret Liotta, Sarah Roord, Charles Berry, Lauren M. Pachman, Alberto Martini, Salvatore Albani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

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) Vβ 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 Vβ gene usage. Conclusion. These findings represent the first identification of a self epitope in juvenile DM, providing a potential candidate for antigen-specific immune therapy.

Original languageEnglish (US)
Pages (from-to)3015-3025
Number of pages11
JournalArthritis and rheumatism
Volume46
Issue number11
DOIs
StatePublished - Nov 1 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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