Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9264328 | Human Immunology | 2005 | 11 Pages |
Abstract
The basic phosphoprotein 150 (pp150), the product of UL32 (unique long domain 32) gene of human cytomegalovirus (CMV), is an abundant component of the viral tegument and a target of human leukocyte antigen (HLA)-restricted cytotoxic T cells (CTLs) after infection. Identification of minimal cytotoxic epitopes (MCEs) from this CMV protein is of importance for peptide-based vaccines and immunotherapeutic approaches. Several pp150-specific CTL clones were derived from peripheral blood mononuclear cells of healthy CMV-positive donors with autologous fibroblasts infected either with CMV AD169 or with a recombinant vaccinia virus expressing full-length pp150 protein. HLA A*0301- and HLA A*6801-restricted CD8+ pp150 T-cell clones derived from different donors were found to efficiently kill autologous CMV-infected fibroblasts. Fine mapping of each MCE first used a T-cell epitope prediction algorithm. Overlapping peptides within the recognized regions were screened. The analysis identified pp150792-802 and pp150945-955 as MCEs for the HLA A*6801 and the HLA A*0301 pp150 clones, respectively. In vitro stimulation by recombinant modified vaccinia Ankara virus expressing full-length pp150 elicited high frequencies of CMV-CTL and interferon gamma production specific for the MCE identified in all subjects. The consistent presence of pp150 T cells in CMV-exposed individuals supports a role for this antigen in shaping the antiviral CTL response and indicates that pp150 could be a pivotal constituent of prophylactic and therapeutic CMV vaccines.
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Authors
Corinna La Rosa, Zhongde Wang, Simon F. Lacey, Susan F. Markel, Madeva C. Sharma, Joybelle Martinez, Maria M. Lalimarmo, Don J. Diamond,