Rheumatic heart disease (RHD) is a severe autoimmune sequela of Group A Streptococcus (GAS) infections and represents a leading cause of mortality in low-income countries. A prevailing theory of RHD pathogenesis suggests that molecular mimicry between GAS M proteins and human cardiac antigens drives the production of cross-reactive antibodies. However, the precise targets of these antibodies remain inadequately defined, and accumulating evidence suggests that RHD pathogenesis involves mechanisms beyond molecular mimicry alone. To elucidate the nature of the autoantibodies involved in RHD onset, we constructed sequences of 20+ historically described antibodies derived from mice immunised with GAS antigens or isolated from RHD patients. Each antibody was expressed in two forms: somatically hypermutated form and reverted germline form. This allowed us to characterize their binding profiles against a diverse panel of protein and peptide antigens implicated in both the protective response to GAS and the pathogenesis of RHD. Our data revealed significant variability in the binding profiles of these antibodies. Some antibodies exhibited concurrent increases in both foreign and self-binding within the immune response, consistent with the concept of molecular mimicry. However, many displayed heterogenous binding patterns, which may be attributed to mechanisms such as self-tolerance and clonal redemption. Notably, many antibodies showed evidence of polyreactivity, especially those unmutated or minimally mutated in their post-immune states, implying the potential involvement of polyreactive germline antibodies in RHD pathogenesis. These findings highlight the complexity of the mechanisms underlying the autoantibody development in RHD and provide insights into the immunogenicity of GAS vaccine candidates.