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Identification of HLA-A*2402-restricted HCMV immediate early-1 (IE-1) epitopes as targets for CD8+ HCMV-specific cytotoxic T lymphocytes

Authors
 Jong-Baeck Lim  ;  Hyun Ok Kim  ;  Seok Hoon Jeong  ;  Joo Eun Ha  ;  Sunphil Jang  ;  Sang-Guk Lee  ;  Kyungwon Lee  ;  David Stroncek 
Citation
 JOURNAL OF TRANSLATIONAL MEDICINE, Vol.7 : 72, 2009 
Journal Title
 JOURNAL OF TRANSLATIONAL MEDICINE 
Issue Date
2009
MeSH
Amino Acid Sequence ; CD8-Positive T-Lymphocytes/immunology* ; CD8-Positive T-Lymphocytes/virology ; Cell Line ; Cytomegalovirus/immunology* ; Cytomegalovirus Infections/immunology ; Cytomegalovirus Infections/therapy ; Epitopes/genetics ; Epitopes/immunology* ; Fibroblasts/cytology ; Fibroblasts/immunology ; HLA-A Antigens/immunology* ; HLA-A24 Antigen ; Humans ; Immediate-Early Proteins/genetics ; Immediate-Early Proteins/immunology* ; Interferon-gamma/immunology ; Molecular Sequence Data ; Peptides/genetics ; Peptides/immunology ; T-Lymphocyte Subsets/immunology* ; T-Lymphocyte Subsets/virology ; T-Lymphocytes, Cytotoxic/immunology* ; T-Lymphocytes, Cytotoxic/virology ; Viral Proteins/genetics ; Viral Proteins/immunology
Keywords
HCMV Infection ; Adoptive Immunotherapy ; Immunogenic Epitope ; Pepro Tech ; HCMV Disease
Abstract
BACKGROUND: To identify novel HLA-A*2402-restricted human cytomegalovirus (HCMV) immediate early-1 (IE-1) epitopes for adoptive immunotherapy, we explored 120 overlapping 15-amino acid spanning IE-1. METHODS: These peptides were screened by measuring the frequency of polyclonal CD8+ T cells producing intracellular interferon-gamma (IFN-gamma) using flow cytometry and the epitopes were validated with a HCMV-infected target Cr release cytotoxicity assay. RESULTS: Initial screening was performed with 12 mini-pools of 10 consecutive peptides made from 120 overlapping peptides15-amino acids in length that spanned IE-1. When peripheral blood mononuclear cells (PBMCs) from HLA-A*2402 HCMV-seropositive donors were sensitized with each of the 12 mini-pools, mini-pools 1 and 2 induced the highest frequency of CD8+ cytotoxic T lymphocytes (CTLs) producing IFN-gamma. When PBMCs were stimulated with each of the twenty peptides belonging to mini-pools 1 and 2, peptides IE-11-15MESSAKRKMDPDNPD and IE-15-19AKRKMDPDNPDEGPS induced the greatest quantities of IFN-gamma production and cytotoxicity of HLA-matched HCMV-infected fibroblasts. To determine the exact HLA-A*2402-restricted epitopes within the two IE-1 proteins, we synthesized a total of twenty-one overlapping 9- or 10 amino acid peptides spanning IE-11-15 and IE-15-19. Peptide IE-13-12SSAKRKMDPD induced the greatest quantities of IFN-gamma production and target cell killing by CD8+ CTLs. CONCLUSION: HCMV IE-13-12SSAKRKMDPD is a HLA-A*2402-restricted HCMV IE-1 epitope that can serve as a common target for CD8+ HCMV-specific CTLs.
Files in This Item:
T200903013.pdf Download
DOI
10.1186/1479-5876-7-72
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Hyun Ok(김현옥) ORCID logo https://orcid.org/0000-0002-4964-1963
Lee, Kyungwon(이경원) ORCID logo https://orcid.org/0000-0003-3788-2134
Lee, Sang-Guk(이상국) ORCID logo https://orcid.org/0000-0003-3862-3660
Lim, Jong Baeck(임종백) ORCID logo https://orcid.org/0000-0003-0419-0422
Jang, Sun Phil(장선필)
Jeong, Seok Hoon(정석훈) ORCID logo https://orcid.org/0000-0001-9290-897X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/104577
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