Analysis of the human cytomegalovirus pp65-directed T-cell response in healthy HLA-A2-positive individuals
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Juliane Schalich
Abstract
Human cytomegalovirus (HCMV) is contained by T-lymphocyte responses focused towards the major tegument protein pp65. To systematically identify T-cell epitopes, we applied the following strategy: 441 overlapping 15mer peptides spanning the entire HCMV pp65 antigen in 1-aa steps were screened in enzyme-linked immunospot (ELIspot) assays for interferon gamma (IFN-γ) secretion by peripheral blood mononuclear cells (PBMCs) from nine healthy HCMV-seropositive subjects expressing human leukocyte antigen (HLA)-A2. This analysis confirmed a number of previously known epitopes and revealed several new ones. A total of 26 epitopes were identified, including 14 HLA-A2, four HLA-B7, -B35, -B12 and -B44 restricted class I epitopes, six class II epitopes, and two epitopes of unknown restriction. Three novel HLA-A2 epitopes were confirmed using T2-cells, and one peptide for which only binding data had been published so far was verified. Two novel class II epitopes were confirmed by intracellular cytokine staining. Responses were usually oligoclonal against up to seven HLA-A2 epitopes, albeit with a few dominating epitopes. Clusters of overlapping epitopes (hot-spots) were identified. These and the newly identified T-cell epitopes may be of great value for epitope-based immunotherapeutic approaches, including peptide vaccines.
©2008 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Guest Editorial
- Novel paradigms in vaccine development: from small pox eradication to therapeutic vaccines
- Highlight: 3rd Semmering Conference 2007
- Adaptive immune responses to hepatitis C virus: from viral immunobiology to a vaccine
- Dendritic cell subtypes as primary targets of vaccines: the emerging role and cross-talk of pattern recognition receptors
- Novel strategies to identify biomarkers in tuberculosis
- Not to wake a sleeping giant: new insights into host-pathogen interactions identify new targets for vaccination against latent Mycobacterium tuberculosis infection
- Lipopolysaccharide: a tool and target in enterobacterial vaccine development
- The coming of age of virus-like particle vaccines
- Maintenance of serological memory
- Adjuvant activity of type I interferons
- Japanese encephalitis vaccines – needs, flaws and achievements
- Analysis of the human cytomegalovirus pp65-directed T-cell response in healthy HLA-A2-positive individuals
- Non-regulatory CD8+CD45RO+CD25+ T-lymphocytes may compensate for the loss of antigen-inexperienced CD8+CD45RA+ T-cells in old age
- Pre-clinical development of cell culture (Vero)-derived H5N1 pandemic vaccines
- Construction of an encapsulated ESAT-6-based anti-TB DNA vaccine and evaluation of its immunogenic properties
- Review
- RNA switches regulate initiation of translation in bacteria
- Protein Structure and Function
- Inhibition of bacterial oxidases by formamide and analogs
- Modeling of variant copies of subunit D1 in the structure of photosystem II from Thermosynechococcus elongatus
