Rheumatic fever following group A streptococcal infections is an example of which autoimmune mechanism?

• A. Epitope spreading
• B. Molecular mimicry
• C. Polyclonal B cell activation
• D. Preferential activation of T-helper cells

Answer: (B)

Molecular mimicry is at play when the immune system responds to group A Streptococcus and creates antibodies that cross-react with heart tissue because the bacterial and human proteins share similar structural features. The antibodies targeting the bacterial M protein can also bind cardiac proteins such as myosin and valve components, triggering inflammation in the heart weeks after the infection. This cross-reactive response is the classic driver of rheumatic fever, combining antibody- and T-cell–mediated damage to the heart.

Epitope spreading would mean the immune response expands to additional self-epitopes after the initial trigger, which isn’t the primary driver in this scenario. Polyclonal B cell activation would produce a broad range of antibodies without the specific cross-reactivity to heart tissue. Preferential activation of T-helper cells implies a bias in helper T cell responses, but the defining mechanism here is cross-reactivity from molecular mimicry between pathogen and host antigens.