ArticleProceedings of the National Academy of Sciences of the United States of America2015
Physical detection of influenza A epitopes identifies a stealth subset on human lung epithelium evading natural CD8 immunity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
34 citing papers in PubMed, 51 citations in OpenAlex.
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- Influenza Virus-Derived CD8 T Cell Epitopes: Implications for the Development of Universal Influenza Vaccines.Immune network · 2024Review
- Harnessing αβ T cell receptor mechanobiology to achieve the promise of immuno-oncology.Proceedings of the National Academy of Sciences of the United States of America · 2023Review
- A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design.The Journal of experimental medicine · 2023Article
- Workflow enabling deepscale immunopeptidome, proteome, ubiquitylome, phosphoproteome, and acetylome analyses of sample-limited tissues.Nature communications · 2023Article
- Lynch syndrome cancer vaccines: A roadmap for the development of precision immunoprevention strategies.Frontiers in oncology · 2023Review
- A bead-based method for high-throughput mapping of the sequence- and force-dependence of T cell activation.Nature methods · 2022Article
- Improved T-cell Immunity Following Neoadjuvant Chemotherapy in Ovarian Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Reversal of viral and epigenetic HLA class I repression in Merkel cell carcinoma.The Journal of clinical investigation · 2022Article
- TCR-mimic bispecific antibodies to target the HIV-1 reservoir.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Immunopeptidomic analysis of influenza A virus infected human tissues identifies internal proteins as a rich source of HLA ligands.PLoS pathogens · 2022Article
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- Optimized Liquid and Gas Phase Fractionation Increases HLA-Peptidome Coverage for Primary Cell and Tissue Samples.Molecular & cellular proteomics : MCP · 2021Article
- Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial.Nature · 2019Article
- Plant-derived virus-like particle vaccines drive cross-presentation of influenza A hemagglutinin peptides by human monocyte-derived macrophages.NPJ vaccines · 2019Article
- Cancer Neoepitopes for Immunotherapy: Discordance Between Tumor-Infiltrating T Cell Reactivity and Tumor MHC Peptidome Display.Frontiers in immunology · 2019Article
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- αβ T Cell Receptor Mechanosensing Forces out Serial Engagement.Trends in immunology · 2018Review
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6 authors at 4 institutions in 2 countries.
Funding
Abstract
Vaccines eliciting immunity against influenza A viruses (IAVs) are currently antibody-based with hemagglutinin-directed antibody titer the only universally accepted immune correlate of protection. To investigate the disconnection between observed CD8 T-cell responses and immunity to IAV, we used a Poisson liquid chromatography data-independent acquisition MS method to physically detect PR8/34 (H1N1), X31 (H3N2), and Victoria/75 (H3N2) epitopes bound to HLA-A*02:01 on human epithelial cells following in vitro infection. Among 32 PR8 peptides (8-10mers) with predicted IC50 < 60 nM, 9 were present, whereas 23 were absent. At 18 h postinfection, epitope copies per cell varied from a low of 0.5 for M13-11 to a high of >500 for M1(58-66) with PA, HA, PB1, PB2, and NA epitopes also detected. However, aside from M1(58-66), natural CD8 memory responses against conserved presented epitopes were either absent or only weakly observed by blood Elispot. Moreover, the functional avidities of the immunodominant M1(58-66)/HLA-A*02:01-specific T cells were so poor as to be unable to effectively recognize infected human epithelium. Analysis of T-cell responses to primary PR8 infection in HLA-A*02:01 transgenic B6 mice underscores the poor avidity of T cells recognizing M1(58-66). By maintaining high levels of surface expression of this epitope on epithelial and dendritic cells, the virus exploits the combination of immunodominance and functional inadequacy to evade HLA-A*02:01-restricted T-cell immunity. A rational approach to CD8 vaccines must characterize processing and presentation of pathogen-derived epitopes as well as resultant immune responses. Correspondingly, vaccines may be directed against "stealth" epitopes, overriding viral chicanery.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.