Early T Cell Recognition of B Cells following Epstein-Barr Virus Infection: Identifying Potential Targets for Prophylactic Vaccination

Epstein-barr virus,a b-lymphotropic herpesvirus,is the cause of infectious mononucleosis,has strong aetiologic links with several malignancies and has been implicated in certain autoimmune diseases. efforts to develop a prophylactic vaccine to prevent or reduce ebv-associated disease have,to date,focused on the induction of neutralising antibody responses. however,such vaccines might be further improved by inducing t cell responses capable of recognising and killing recently-infected b cells. in that context,ebna2,ebna-lp and bhrf1 are the first viral antigens expressed during the initial stage of b cell growth transformation,yet have been poorly characterised as cd8+ t cell targets. here we describe cd8+ t cell responses against each of these three “first wave” proteins,identifying target epitopes and hla restricting alleles. while ebna-lp and bhrf1 each contained one strong cd8 epitope,epitopes within ebna2 induced immunodominant responses through several less common hla class i alleles (e.g. b*3801 and b*5501),as well as subdominant responses through common class i alleles (e.g. b7 and c*0304). importantly,such ebna2-specific cd8+ t cells recognised b cells within the first day post-infection,prior to cd8+ t cells against well-characterised latent target antigens such as ebna3b or lmp2,and effectively inhibited outgrowth of ebv-transformed b cell lines. we infer that “first wave” antigens of the growth-transforming infection,especially ebna2,constitute potential cd8+ t cell immunogens for inclusion in prophylactic ebv vaccine design. © 2016 brooks et al.