BSLF2/BMLF1

Epstein-Barr virus (EBV), also called human herpesvirus 4 (HHV-4), is a genetically stable agent that has slowly co-evolved with our species and its antecedents for millions of years. EBV is typically transmitted orally during childhood, propagates in B cells and epithelia, and is shed for the lifetime of the host. More than 90% of the world's population is infected with EBV. This mutual coexistence is not without heavy resource cost for the host. Large populations of CD8+ αβ T lymphocytes are deployed for the purposes of EBV surveillance and suppression. These populations peak during asymptomatic primary infection, acute infectious mononucleosis (AIM) and old age. Across the entire EBV proteome, one of the most immunogenic CD8+ T cell targets is the HLA-A*0201-restricted GLCTLVAML peptide derived from the BMLF1 protein (residues 280–288; herein referred to as GLC-A2). During primary infection, up to 11% of the total peripheral CD8+ T cell pool can be specific for GLC-A2; this response contracts to 0.5–2.2% of the peripheral CD8+ T cell pool during persistent infection, but can swell again to 10% in old age. Given the high in vivo frequencies of this response and the ubiquity of both EBV infection and the HLA-A*0201 allele, it is unsurprising that GLC-A2 is one of the most studied HLA class-I target antigens. Interestingly, initial investigations into the clonotypic nature of the GLC-A2 response revealed that CD8+ T cells are deployed with a biased T cell receptor (TCR) repertoire that is stable over time.