What drives the human immune system's fight against Epstein-Barr virus? This review dives into cytotoxic T lymphocyte (CTL) responses in humans, using Epstein-Barr virus (EBV) as a highly informative model. EBV establishes a highly immunogenic growth-transforming infection of B lymphocytes, inducing the expression of six virus-coded nuclear antigens (EBNAs) and two latent membrane proteins (LMPs). This triggers both primary and memory CD8+ CTL responses, skewed towards HLA allele-specific epitopes drawn from the EBNA3A, 3B, 3C subset of latent proteins. Other antigens elicit far less frequent responses. Furthermore, CTLS to some of the immunodominant epitopes may cause TCR usage, which suggest could have immunopathological consequences from cross-reactive recognition of other target structures. Targeting EBV-associated tumors, dramatic reversals of EBV-driven lymphoproliferations have been observed in transplant patients following CTL infusion. The review explores the potential of this approach for other EBV-positive tumors lacking EBNA3A, 3B, 3C proteins. It offers insights into EBV-associated malignancies and CTL-based therapeutic strategies.
Published in Annual Review of Immunology, this paper clearly fits the journal's mission by providing a comprehensive overview of CTL responses to EBV infection, a major topic in human immunology. The review's focus on the EBNA3A, 3B, and 3C proteins, their immunodominance, and potential therapeutic applications is of significant interest to the journal's readership.