Highly translated EBNAGA induces a stronger T cell response.

Most viral epitopes are derived not from long-lived stable proteins but from defectively translated and rapidly degraded intermediates. More translation should lead to more intermediates and thus more epitope presentation. However, this link has not been convincingly shown with identical proteins that have different translation efficiencies.

Tellam and colleagues compared cells translating either EBNA1 from Epstein-Barr virus (EBV), or a mutant version of EBNA1 that lacked EBNA1's self-inhibiting sequence and was therefore translated more rapidly.

Cells expressing the normal EBNA1 generated very few epitopes and failed to activate T cells. In contrast, cells expressing the mutant EBNA1 produced a large number of epitopes, possibly due to the production of more defective products, and primed a strong T cell response.

EBV evades the immune response by minimizing EBNA1 translation and thus presentation; EBNA1 also inhibits its own degradation so that normal levels of protein are maintained. In EBV-associated cancers, increasing EBNA1 translation rates by targeting EBNA1's self-inhibiting sequence may lead to increased epitope presentation and thus improve the efficacy of cancer therapies using anti-EBV T cells.