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Identification of HLA-A33-restricted CMV pp65 epitopes as common targets for CD8+ CMV-specific cytotoxic T lymphocytes

Authors
 Jong-Baeck Lim  ;  Maurizio Provenzano  ;  Oh Hun Kwon  ;  Maria Bettinotti  ;  Lorraine Caruccio  ;  Dirk Nagorsen  ;  David Stroncek 
Citation
 EXPERIMENTAL HEMATOLOGY, Vol.34(3) : 296-307, 2006 
Journal Title
EXPERIMENTAL HEMATOLOGY
ISSN
 0301-472X 
Issue Date
2006
MeSH
Amino Acid Sequence ; CD8-Positive T-Lymphocytes/immunology* ; Epitopes/chemistry ; Epitopes/immunology* ; Flow Cytometry ; HLA-A Antigens/immunology* ; Humans ; Immunologic Memory ; Interferon-gamma/biosynthesis ; Interferon-gamma/genetics ; Molecular Sequence Data ; Phosphoproteins/immunology* ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Viral Matrix Proteins/immunology*
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-gamma (IFN-gamma) 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-gamma mRNA transcript from CMV-seropositive HLA-A33 peripheral blood mononuclear cells. All the eight peptides induced consistent T-cell reactivation. One specifically, the peptide pp65(91-100) (SVNVHNPTGR), proved to be more active. T cells in vitro sensitized for 2 or 3 weeks with pp65(91-100) 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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0301472X05005679
DOI
10.1016/j.exphem.2005.12.006
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Oh Hun(권오헌)
Lim, Jong Baeck(임종백) ORCID logo https://orcid.org/0000-0003-0419-0422
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108768
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