To analyze the immune response to the C region of group A streptococcal M protein in patients with rheumatic fever (RF), we cloned the structural gene for the C region of type 12 M protein and produced recombinant C region of M protein. IgG titers against the C region of M protein were measured by ELISA from sera of patients with RF (n = 10), uncomplicated streptococcal pharyngitis (n = 26), and age-matched controls (n = 49). IgG titers against the C-region were significantly higher in patients with RF than in controls or patients with uncomplicated streptococcal pharyngitis (43 versus 1.5 or 1.8 μg/mL, p < 0.01). Studies using overlapping synthetic peptides of the C region demonstrated that increased IgG reactivity was observed against the amino-terminal halves of the C repeat blocks (C1, C2) in RF, indicating that these domains are the main immunodominant epitopes in the C region.
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