A single amino acid substitution in a self protein is sufficient to trigger autoantibody response

Y. Tsujihata, T. So, Y. Hashimoto, Tadashi Ueda, T. Imoto

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8 Citations (Scopus)


We determined if a single amino acid substitution in a self protein causes autoantibody responses. Mouse lysozyme (ML) was used as a model self protein, and a mutant ML (F57L ML) was prepared by replacing 57Phe of ML to Leu, an approach which resulted in introducing into ML the immunogenic sequence of peptide 50-61 of hen egg lysozyme (HEL) restricted to I-Ak MHC class II molecule. We found that F57L ML but not native ML primed HEL specific T cells and triggered ML specific autoantibody responses in B10.A and C3H mice (I-Ak, I-Ek). Peptide regions, ML 14-69 and ML 98-130, were major epitopes of autoantibodies in both strains of mice. These findings indicate that a single amino acid substitution in self proteins can cause an autoantibody response when the mutated region is presented by MHC class II molecules and recognized by T cells.

Original languageEnglish
Pages (from-to)375-381
Number of pages7
JournalMolecular Immunology
Issue number5
Publication statusPublished - Nov 7 2001


All Science Journal Classification (ASJC) codes

  • Immunology
  • Molecular Biology

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