Identification of immunogenic epitopes of β-adrenergic receptor 1 that induce heart autoimmunity in A/J mice (BA8P.164)

Abstract

Abstract Coxsackievirus B3 (CVB3) is one of the important infectious causes of myocarditis that may lead to dilated cardiomyopathy. To study the autoimmune events in this viral infection, various mouse models are commonly employed. In our studies with A/J mice, we recently demonstrated that the animals infected with CVB3 show the appearance of pathogenic T cells specific to cardiac myosin heavy chain (Myhc)-alpha 334-352, leading us to hypothesize that CVB3 infection might accompany with the generation of T cells with specificities for multiple antigens. To test this hypothesis, we sought to identify the immunogenic epitopes of one other putative cardiac antigen namely, β-adrenergic receptor 1 (BAR1) that has been previously implicated in the immune pathogenesis of CVB3 infection. Our data revealed that the peptides spanning the amino acids, 170 to 230 are capable of inducing epi/endocarditis by active immunization. We also noted that the disease induced by BAR1-peptides was associated with the induction of CD4 and/or CD8 T cell responses, with a skewed T helper (Th)1 and Th17 cytokine production. In conjunction with Myhc-alpha 334-352, identification of BAR1-peptides may thus permit us to determine the kinetics of the generation of autoreactive T cells with multiple antigen-specificities, which might be generated as a result of epitope spreading during the course of CVB3 infection.