Despite accumulating epidemiological and histopathological evidence for an association between Coxsackievirus B (CVB) and type 1 diabetes (T1D), a causal link is missing. Very little is known about the T-cell response mounted against CVB infection and the epitopes targeted. Moreover, the ongoing CVB vaccination trials require: 1) the development of T-cell biomarkers to follow vaccination efficacy; and 2) the exploration of potential cross-reactivities with islet antigens that may precipitate rather than prevent T1D. We identified the HLA Class I viral peptidome of CVB-infected β cells, pinpointed a highly focused response toward very few immunodominant epitopes recognized by CD8+ T cells, and the functional features of these T cells, e.g. their capacity to destroy infected beta cells.
We now aim to investigate whether these CD8+ T cells recognizing CVB peptides are also found in the pancreatic tissues targeted by islet autoimmunity, and whether they are enriched in these tissues as compared to peripheral ones. Such enrichment would lend support to the role of CVB infection in triggering islet autoimmunity.