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Sustained CD8 + T‐cell immune response to a novel immunodominant HLA‐B * 0702‐associated epitope derived from an Epstein–Barr virus helicase‐primase‐associated protein
Author(s) -
Turčanová Vanda,
Höllsberg Per
Publication year - 2004
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.20023
Subject(s) - epitope , cytotoxic t cell , virology , biology , elispot , cd8 , immune system , t cell , human leukocyte antigen , antigen , immunology , in vitro , genetics
Generation of a peptide‐based vaccine against persistent viral infections, such as Epstein–Barr virus (EBV), requires identification of immunodominant epitopes recognized by anti‐viral cytotoxic T‐cells. Using available computer algorithms, we have screened the entire translated EBV genome for potential HLA‐B7‐binding peptides. The binding to HLA‐B7 of 18 selected peptides was assessed by competitive binding assays and was found to correlate with the computer‐assigned scores, confirming the predictive value of these algorithms in selection of HLA‐B7‐associated peptides. Screening of the immune responses to these peptides by ELISpot assays identified a novel immunodominant epitope, termed LPRA, derived from an EBV helicase‐primase‐associated protein encoded by BBLF2/3. Peptide‐specific cells constituted up to 0.8% LPRA‐specific CD8 + T‐cells in the matured anti‐viral response. Cytotoxic and proliferative cytotoxic T lymphocytes (CTL) responses to the LPRA peptide were readily demonstrated ex vivo. In addition, mutational studies of this epitope demonstrated a highly specific recognition by LPRA‐specific CD8 + T‐cells. Taken together, our data suggest that the novel lytic‐phase HLA‐B7‐associated epitope contains essential features required of a component in an EBV peptide‐based vaccine. J. Med. Virol. 72:635–645, 2004. © 2004 Wiley‐Liss, Inc.