Epstein-barr virus nuclear antigen 1: from immunologically invisible to a promising T cell target

Abstract

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1)--the one EBV antigen that is expressed in all EBV-associated malignancies--has long been thought to go undetected by the cell-mediated immune system. However, recent studies show that EBNA1 can be presented to both CD4+ and CD8+ T cells, making it a potential new target for immunotherapy of EBV-related cancers.

Figure 1.

Suggested antigen processing pathways of EBNA1. (A) Defective ribosomal products (DRiPs) of EBNA1 are degraded by the proteasome for MHC class I presentation (endogenous MHC class I antigen processing). (B) Full-length EBNA1 is not degraded by the proteasome and might be the source of MHC class II ligands (endogenous MHC class II antigen processing). (C) EBNA1 released by dying EBV-transformed B cells is taken up by APCs and presented for CD4⁺ and CD8⁺ T cell priming (exogenous MHC class I and II antigen processing).