IDENTIFICATION OF TYPE B-SPECIFIC AND CROSS-REACTIVE CYTOTOXIC T-LYMPHOCYTE RESPONSES TO EPSTEIN-BARR-VIRUS

Persistent Epstein-Barr virus (EBV) infection is primarily controlled by HLA class I-restricted memory cytotoxic T-cell (CTL) responses whic h can be reactivated in vitro by stimulation of peripheral blood lymph ocytes with autologous lymphoblastoid cell Lines. During an investigat ion of a donor infected by both type A and type B EBV, CTL specific fo r type B EBV were isolated. The CTL were found to recognize an epitope encoded by the EBNA-6B gene. The minimal epitope sequence was identif ied as QNGALAINTF, corresponding to residues 213 to 222 in the EBNA-6B protein, and presentation of this epitope was shown to be via HLA B62 (B15). This is the first report of the characterization of an epitope that is EBV type B specific, CTL recognizing sequences common to type A and type B EBV were identified as well. A cross-reactive epitope re cognized by these CTL was encoded within the EBNA-6 gene of both type A and type B, This minimal sequence for this epitope was LLDFVRFMGV (r esidues 254 to 293 in bath types), and the epitope was restricted thro ugh HLA A0201. This second epitope sequence overlaps with a published EBV B44-restricted epitope (EENLLDFVRF). The implications of these fi ndings are discussed with respect to the design and efficacy of epitop e-based vaccines.