Similarity to Self-Antigens Shapes Epitope Recognition from Viruses Under Autoimmune and Infectious Disease

Self/non-self-discrimination is a fundamental aspect of adaptive immunity, which helps prevent harmful autoimmune responses. However, infectious agents can also act as environmental catalysts for autoimmune diseases. In this study, we investigated the role of molecular mimicry to self-antigens in epitope recognition in relation to infectious and autoimmune diseases. To this end, we performed BLAST searches against the human proteome, utilizing known virus-specific B and T cell peptide epitopes identified in association with autoimmune or infectious diseases in humans as our queries. Additionally, similar control analyses were carried out using non-B and non-T cell epitopes, consisting of random viral peptide sequences. Overall, our results endorsed a major role of molecular mimicry in instigating or sustaining autoimmunity associated with viral infections and challenged the prevailing view on self/non-self-discrimination for T cells. Additionally, we uncovered many virus-specific epitopes among those identified in association with infectious diseases with high similarity to self-antigens, which are primarily derived from human coronaviruses and various flaviviruses. Recognition of these epitopes could lead to autoimmunity against human proteins that are in cellular components concerning cell motility, cell membrane projections, and cellular synapses.