A single amino acid substitution in a self protein is sufficient to trigger autoantibody response.
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-A(k) 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-A(k), I-E(k)). 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.
Tsujihata
Y
Y
Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan.
So
T
T
Hashimoto
Y
Y
Ueda
T
T
Imoto
T
T
D019943:Amino Acid Substitution; D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D005260:Female; D007930:Leucine / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009113:Muramidase / Q000235:genetics / Q000276:immunology*; D016297:Mutagenesis, Site-Directed; D010649:Phenylalanine / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D010649:Phenylalanine; C421864:hen egg lysozyme; D009113:Muramidase; D007930:Leucine