Through a series of experiments assessing the development of HRS-induced myositis in C57BL/6-derived strains lacking specific components of innate and/or adaptive immune signaling pathways, we have shown that antigen-specific TCR engagement and MyD88-directed innate immune signaling cascades are both required for maximal T cell infiltration and expression of the myositis tissue phenotype. The gene discussed is MYD88; the disease is myositis disease.