The Role of EBNA Proteins as a Target for EBV-Specific T Cell Lysis

Summary

Studies in recent years have focussed on EBNA proteins as a major site of LYDMA molecules. Two separate technologies have demonstrated that EBNA proteins include CTL epitopes. Firstly, recombinant vaccinia viruses have been constructed containing coding sequences for four EBNA proteins and we have used these to demonstrate that CTL epitopes are included in EBNAs 2, 3 and 6. Secondly, by selecting EBNA peptides for amphipathic helical sequences and by screening these peptides with CTL clones we have defined three CTL epitopes at the peptide level. The first is included in EBNA3 (referred to as TETA), the second is included in EBNA6 (referred to as EENL) and the third is included in EBNA2 (referred to as QLSD). The TETA sequence has been investigated in detail by preparing a peptide “window” and has shown that the minimal epitope sequence is a 9 mer and has highlighted two amino acids that are essential for activity. The variation in TETA sequences between different EBV isolates has been demonstrated using PCR. The most important finding is that there is very significant heterogeneity in the TETA sequence between different EBV isolates.