A chimeric HLA-A2:β2M:Ig fusion protein for the study of virus-specific CD8+ T-cells

dc.creatorRibeiro, Ágata Lopes
dc.creatorAraújo, Franklin Pereira
dc.creatorMartins, Julia Pereira
dc.creatorLourenço, Alice Aparecida
dc.creatorHuang, Jing
dc.creatorPereira, Felipe Valença
dc.creatorAndrade, Luis Adan Flores
dc.creatorPaim, Adriana Alves Oliveira
dc.creatorFonseca, Flávio Guimarães da
dc.creatorStancioli, Edel Figueiredo Barbosa
dc.creatorMartins Filho, Olindo Assis
dc.creatorPascoal, Vanessa Peruhype Magalhães
dc.creatorTsuji, Moriya
dc.creatorReis, Jordana Grazziela Coelho dos
dc.date2022-02-10T16:22:53Z
dc.date2022-02-10T16:22:53Z
dc.date2021
dc.date.accessioned2023-09-26T21:06:05Z
dc.date.available2023-09-26T21:06:05Z
dc.identifierRIBEIRO, Ágata Lopes et al. A chimeric HLA-A2:β2M:Ig fusion protein for the study of virus-specific CD8+ T-cells. Journal of Immunological Methods, v. 492, 112997, 2021. doi.org/10.1016/j.jim.2021.112997
dc.identifier0022-1759
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/51135
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8869157
dc.descriptionIntroduction: The response mediated by CD8+ T-cells in the context of infection and vaccination has been thoroughly investigated and represents one of the most important branches that allow for the development of immunity against intracellular pathogens and, thus, the establishment of robust antiviral responses. However, there is a lack of methods to assess antigen-specific CD8+ T-cells. Objective: Search for the ideal assays to assess the function of antigen-specific CD8+ T-cells. Methods: In the present study a chimeric HLA-A2:β2M:Ig fusion protein was produced, purified, and evaluated in functional CD8+ T-cell response studies using samples from Influenza A patients and humanized mice upon adenoviral vaccination. Results: The HLA-A2:β2M:Ig molecule, bound to immunodominant viral peptides by passive transfer, was able to induce robust antiviral CD8+ T-cell responses mediated by IFN-γ. The in vitro IFN-γ release assay using the chimeric HLA-A2:β2M:Ig fusion protein detected bona fide human CD8+ T-cells, demonstrating superior production of IFN-γ by human CD8+ T-cells induced by Influenza A immunodominant GILGFVFTL peptide. Removal of antigen-presenting cells and CD8+ T-cell enrichment improved significantly the IFN-γ production. The chimeric HLA-A2:β2M:Ig fusion protein also triggered HLA-A2-restricted CD8+ T-cell response in a humanized mouse model upon vaccination with adenovirus encoding HLA-A2-restricted HIV p24 antigen. The results strongly suggest the use of tailor-made assays for detecting HLA-A2-restricted CD8+ T-cell Responses in the Humanized Mouse Model. Conclusion: The chimeric HLA-A2:β2M:Ig fusion protein-based assays provided a sensitive tool that may be paramount to measure virus-specific CD8+ T-cell response in a range of viral infections of clinical relevance.
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier B.V. All
dc.rightsrestricted access
dc.subjectChimeric HLA-A2:β2M:Ig protein
dc.subjectHLA-A2-restricted peptides
dc.subjectntiviral CD8+ T-cell response
dc.subjectHumanized mice model
dc.titleA chimeric HLA-A2:β2M:Ig fusion protein for the study of virus-specific CD8+ T-cells
dc.typeArticle


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