Autoimmune disease occurs when (1) there is a breakdown in self-tolerance and (2) the target organ is susceptible to damage by the immune system. Our studies focus on the susceptibility of the target organ to damage. Autoimmune myocarditis is an inflammatory heart disease characterized by myocyte necrosis and an inflammatory infiltrate in the myocardium. Clinically, the disease can range from a mild illness to a serious condition characterized by heart failure, arrhythmias and in some cases can lead to death. Studies in our laboratory have correlated the presence of myosin, or a myosin-like protein, in the extracellular matrix of the heart to disease susceptibility to antibody-mediated myocarditis. Here, we explore what factors determine susceptibility to antibody-induced cardiac damage.