Epitope focusing in the primary cytotoxic T cell response to Epstein-Barr virus and its relationship to T cell memory.

摘要: The relationship between primary and memory cytotoxic T lymphocyte (CTL) responses, the factors influencing entry into memory, are poorly understood. Here we address this in context of Epstein-Barr virus (EBV), a persistent human herpesvirus which CTL responses long-term carriers highly focused on epitopes preferentially drawn from just three eight available latent proteins, EBNAs 3A, 3B, 3C. To determine whether unusual level focusing is consequence challenge, carried out detailed analysis EBV antigen/epitope specificities virus-induced response 10 infectious mononucleosis (IM) patients different HLA types. Primary effectors, studied ex vivo assays by limiting dilution cloning vitro, were again skewed toward small number viral epitopes, almost all derived EBNA3 with to immunodominant epitope accounting for at least 1% circulating CD8+ IM cell pool. This first unequivocal demonstration an EBV-specific IM. Prospective studies individual showed that, whereas reactivities found had been detectable earlier during infection, population was not simply scaled down version response. In particular (a) differences relative frequencies versus subdominant appeared be much less marked than populations, (b) one clear example significant virus-specific reactivity within never memory.