Abstract

The evolution of Epstein‐Barr virus (EBV)–specific T cell responses that occurs during the acute and persistent stages of infection remains poorly characterized despite its importance for developing immune interventions for EBV‐associated disorders. This study assessed T cell responses to 113 EBV‐derived epitopes in 40 subjects with acute or persistent EBV infection. Although no significant differences were seen in the breadth of CD8 and CD4 T cell responses, their magnitude differed significantly over time; acutely infected subjects generated especially strong responses to lytic viral antigens. The cross‐sectional shift in immunodominance was also confirmed in subjects followed longitudinally from acute to persistent infection. In addition, human leukocyte antigen–matched siblings with discordant histories of symptomatic EBV infection showed no significant differences in their response patterns, suggesting that symptomatic EBV infection does not lead to unique persistent‐stage responses. These data provide an assessment of immunodominance patterns and guidance for developing immunotherapeutic interventions for EBV‐associated disorders.

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