T-Cell Receptor Sequences Identify Combined Coxsackievirus- Infections as Triggers for Autoimmune Myocarditis and Coxsackievirus- Infections for Type 1 Diabetes.

Recent research suggests that T-cell receptor (TCR) sequences expanded during human immunodeficiency virus and SARS-CoV-2 infections unexpectedly mimic these viruses. The hypothesis tested here is that TCR sequences expanded in patients with type 1 diabetes mellitus (T1DM) and autoimmune myocarditis (AM) mimic the infectious triggers of these diseases. Indeed, TCR sequences mimicking coxsackieviruses, which are implicated as triggers of both diseases, are statistically significantly increased in both T1DM and AM patients. However, TCRs mimicking antigens are significantly expanded in T1DM, whereas TCRs mimicking antigens are expanded in AM. Notably, antigens mimic T1DM autoantigens, such as insulin and glutamic acid decarboxylase, whereas antigens mimic cardiac autoantigens, such as myosin and laminins. Thus, T1DM may be triggered by combined infections of coxsackieviruses with bacteria, while AM may be triggered by coxsackieviruses with These TCR results are consistent with both epidemiological and clinical data and recent experimental studies of cross-reactivities of coxsackievirus, , and antibodies with T1DM and AM antigens. These data provide the basis for developing novel animal models of AM and T1DM and may provide a generalizable method for revealing the etiologies of other autoimmune diseases. Theories to explain these results are explored.