Identification of an HLA A*0201-restricted CD8(+) T-cell epitope for the glycoprotein B homolog of human herpesvirus 8.

Human herpesvirus 8 (HHV-8; Kaposi sarcoma-associated herpesvirus)-specific cytotoxic T-lymphocyte (CTL) and interferon-gamma (IFN-gamma) responses to proteins produced during the lytic cycle of HHV-8 replication are mediated by HLA class I-restricted, CD8(+) T cells. We have characterized the fine specificity of the CD8(+) T-cell response to 25 peptides derived from 5 HHV-8 lytic cycle proteins based on a prediction model for HLA A*0201 binding motifs. One of the 25 HLA A*0201 peptides derived from the glycoprotein B (gB) homolog of Epstein-Barr virus (gB(492-500); LMWYELSKI; single-letter amino acid codes) bound to HLA A*0201 and stimulated IFN-gamma responses in CD8(+) T cells from HHV-8(+), HLA A*0201 persons, but not HHV-8-seronegative or non-HLA A*0201 persons. The peptide also induced IFN-gamma and CTL reactivity to naturally processed gB protein. The peptide was a major immunogenic epitope of HHV-8 as indicated by induction of IFN-gamma responses in peripheral blood mononuclear cells from 5 of 5 HHV-8 seropositive, HLA A*0201 persons when gB(492-500) was presented by autologous dendritic cells. T-cell reactivity to gB(492-500) was not related to detectable HHV-8 DNA in the blood. These data show that CD8(+) T cells recognize an HLA A*0201-restricted epitope for HHV-8 lytic cycle protein gB, particularly when presented by dendritic cells. This epitope may be important in control of HHV-8 infection by CD8(+) T cells.