Abstract
Objective. To identify an immunodominant HLA-A33-restricted epitope within the CMV matrix phosphoprotein 65 (pp65) that could be used to elicit CMV-specific CTLs. Methods. A computer algorithm was used to identify pp65 peptides that were expected to bind to HLA-A33. The peptides were screened for their ability to reactivate memory T lymphocytes from CMV-seropositive HLA-A33 donors by using quantitative real-time RT-PCR. The most promising peptides were then tested for their ability to expand a CD8+ population of HLA-A33 CTLs that produced interferon-γ (IFN-γ) and were cytotoxic to either peptide-loaded or CMV-infected target cells. Results. Sixteen out of 250 peptides were selected using a computer algorithm and peptide stimulation by 8 out of the 16 induced a significant quantity of IFN-γ mRNA transcript from CMV-seropositive HLA-A33 peripheral blood mononuclear cells. All the eight peptides induced consistent T-cell reactivation. One specifically, the peptide pp6591-100 (SVNVHNPTGR), proved to be more active. T cells in vitro sensitized for 2 or 3 weeks with pp6591-100 were cytotoxic to both HLA-A33 peptide-loaded and CMV-infected target cells. Conclusions. CMV pp65 91-100 is a new HLA-A33-restricted peptide that broadens the list of antigenic determinants that can be used for CMV adoptive immunotherapy.
Original language | English (US) |
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Pages (from-to) | 296-307 |
Number of pages | 12 |
Journal | Experimental Hematology |
Volume | 34 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2006 |
Externally published | Yes |
ASJC Scopus subject areas
- Molecular Biology
- Hematology
- Genetics
- Cell Biology
- Cancer Research