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- W4313368565 abstract "Abstract Cytomegalovirus (CMV)-specific T-cells from healthy donor are used as a treatment of CMV infection in patients receiving immunosuppressive therapy following transplantation. To choose the optimal donor and to select the best isolation method (MHC-tetramer or IFNy secretion assay) CMV-specific T-cells should be characterized by specificity and functionality. We compared the antigen specificity, diversity and functionality of T-cell responding to CMV pp65 and to three pp65-derived immunodominant epitopes: NLV restricted by HLA-A*02, TPR and RPH restricted by HLA-B*07. 87 healthy donors were divided into 4 groups according to the presence of HLA-A*02 and/or HLA-B*07. CMV-specific response was analyzed by flow cytometry. For 6 donors antigen-specific cells were isolated by MHC-tetramer staining and pp65 IFNγ secretion assay followed by FACS. cDNA libraries of T-cell receptor β-chains were prepared and sequenced by NGS. We found that pp65-specific T-cell response (IFNy-producing T-cell after stimulation with pp65 CMV) was strongly focused on pp65-derived epitopes NLV, TPR and RPH in fixed hierarchy. NLV-specific clones constituted most pp65-specific cells in presence of HLA-A*02 but not when HLA-B*07 was also present. NLV-specific fraction consisted of few large clones, TPR− and RPH-specific cells were more diverse. Many MHC-tetramer+ clones were non-functional as they were not detected in IFNy+ fraction after pp65 stimulation. In summary, HLA-genotype significantly affects magnitude and structure of pp65-specific T-cell response. It should be taken into consideration for choosing a donor of CMV-specific T cells. IFNy secretion assay produces more diverse and more functional cell product." @default.
- W4313368565 created "2023-01-06" @default.
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- W4313368565 date "2020-05-01" @default.
- W4313368565 modified "2023-09-27" @default.
- W4313368565 title "Abundance, diversity and functionality of cytomegalovirus-specific T cells depends on HLA genotype of the donor and hierarchy of the immunodominant epitopes" @default.
- W4313368565 doi "https://doi.org/10.4049/jimmunol.204.supp.94.13" @default.
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