Comprehensive Evaluation of the Expressed CD8+ T Cell Epitope Space Using High-Throughput Epitope Mapping
T cell immunity is traditionally assessed through functional recall assays, which detect the consequences of the T cells' antigen encounter, or via fluorescently labeled multimers that selectively bind peptide-specific T cell receptors. Using either approach, if the wrong antigen or peptide of...
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Published in | Frontiers in immunology Vol. 10; p. 655 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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26.04.2019
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Abstract | T cell immunity is traditionally assessed through functional recall assays, which detect the consequences of the T cells' antigen encounter, or via fluorescently labeled multimers that selectively bind peptide-specific T cell receptors. Using either approach, if the wrong antigen or peptide of a complex antigenic system, such as a virus, is used for immune monitoring, either false negative data will be obtained, or the magnitude of the antigen-specific T cell compartment will go largely underestimated. In this work, we show how selection of the "right" antigen or antigenic peptides is critical for successful T cell immune monitoring against human cytomegalovirus (HCMV). Specifically, we demonstrate that individual HCMV antigens, along with previously reported epitopes, frequently failed to detect CD8+ T cell immunity in test subjects. Through systematic assessment of T cell reactivity against individual nonamer peptides derived from the HCMVpp65 protein, our data clearly establish that (i) systematic testing against all potential epitopes encoded by the genome of the antigen of interest is required to reliably detect CD8+ T cell immunity, and (ii) genome-wide, large scale systematic testing of peptides has become feasible through high-throughput ELISPOT-based "brute force" epitope mapping. |
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AbstractList | T cell immunity is traditionally assessed through functional recall assays, which detect the consequences of the T cells' antigen encounter, or via fluorescently labeled multimers that selectively bind peptide-specific T cell receptors. Using either approach, if the wrong antigen or peptide of a complex antigenic system, such as a virus, is used for immune monitoring, either false negative data will be obtained, or the magnitude of the antigen-specific T cell compartment will go largely underestimated. In this work, we show how selection of the “right” antigen or antigenic peptides is critical for successful T cell immune monitoring against human cytomegalovirus (HCMV). Specifically, we demonstrate that individual HCMV antigens, along with previously reported epitopes, frequently failed to detect CD8+ T cell immunity in test subjects. Through systematic assessment of T cell reactivity against individual nonamer peptides derived from the HCMVpp65 protein, our data clearly establish that (i) systematic testing against all potential epitopes encoded by the genome of the antigen of interest is required to reliably detect CD8+ T cell immunity, and (ii) genome-wide, large scale systematic testing of peptides has become feasible through high-throughput ELISPOT-based “brute force” epitope mapping. |
Author | Reche, Pedro A Lehmann, Alexander Zhang, Ting Karulin, Alexey Y Roen, Diana R Lehmann, Paul V Suwansaard, Maneewan Kirchenbaum, Greg A |
AuthorAffiliation | 1 Cellular Technology Ltd. , Shaker Heights, OH , United States 2 Laboratorio de Inmunomedicina & Inmunoinformatica, Departamento de Immunologia & O2, Facultad de Medicina, Universidad Complutense de Madrid , Madrid , Spain |
AuthorAffiliation_xml | – name: 2 Laboratorio de Inmunomedicina & Inmunoinformatica, Departamento de Immunologia & O2, Facultad de Medicina, Universidad Complutense de Madrid , Madrid , Spain – name: 1 Cellular Technology Ltd. , Shaker Heights, OH , United States |
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Cites_doi | 10.1016/S0198-8859(01)00298-1 10.3390/cells4010071 10.1371/journal.pone.0067016 10.4049/jimmunol.167.3.1353 10.1046/j.1365-2567.1999.00901.x 10.3390/cells6040047 10.1128/JVI.70.11.7569-7579.1996 10.1016/S0198-8859(02)00432-9 10.1146/annurev.iy.11.040193.001241 10.1007/s002510000271 10.1016/0092-8674(94)90336-0 10.1007/978-1-61779-325-7_13 10.1111/j.1365-2567.2011.03515.x 10.1371/journal.pone.0084246 10.1016/S0022-2836(03)00750-2 10.1007/s00251-004-0709-7 10.1056/NEJM200009073431006 10.4049/jimmunol.165.3.1278 10.1007/s00251-008-0341-z 10.1084/jem.187.12.2055 10.1007/978-1-60327-118-9_13 10.1016/S0959-440X(99)00039-1 10.3390/cells4010096 10.3390/cells1030313 10.4049/jimmunol.1202281 10.3389/fimmu.2018.02778 10.1002/eji.200737365 10.1016/0167-5699(89)90247-8 10.1146/annurev.immunol.17.1.51 |
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Copyright | Copyright © 2019 Lehmann, Suwansaard, Zhang, Roen, Kirchenbaum, Karulin, Lehmann and Reche. 2019 Lehmann, Suwansaard, Zhang, Roen, Kirchenbaum, Karulin, Lehmann and Reche |
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Keywords | peptide HCMV T cell EBV MHC HLA epitope ELISPOT |
Language | English |
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SubjectTerms | EBV epitope HCMV HLA Immunology MHC peptide |
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Title | Comprehensive Evaluation of the Expressed CD8+ T Cell Epitope Space Using High-Throughput Epitope Mapping |
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