Genetically engineered CD80–pMHC-harboring extracellular vesicles for antigen-specific CD4+ T-cell engagement
The identification of low-frequency antigen-specific CD4+ T cells is crucial for effective immunomonitoring across various diseases. However, this task still encounters experimental challenges necessitating the implementation of enrichment procedures. While existing antigen-specific expansion techno...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1341685/full |
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| author | Irina A. Ishina Inna N. Kurbatskaia Azad E. Mamedov Elena I. Shramova Sergey M. Deyev Sergey M. Deyev Sergey M. Deyev Kamila S. Nurbaeva Yury P. Rubtsov Yury P. Rubtsov Alexey A. Belogurov Alexey A. Belogurov Alexander G. Gabibov Alexander G. Gabibov Alexander G. Gabibov Maria Y. Zakharova Maria Y. Zakharova |
| author_facet | Irina A. Ishina Inna N. Kurbatskaia Azad E. Mamedov Elena I. Shramova Sergey M. Deyev Sergey M. Deyev Sergey M. Deyev Kamila S. Nurbaeva Yury P. Rubtsov Yury P. Rubtsov Alexey A. Belogurov Alexey A. Belogurov Alexander G. Gabibov Alexander G. Gabibov Alexander G. Gabibov Maria Y. Zakharova Maria Y. Zakharova |
| author_sort | Irina A. Ishina |
| collection | DOAJ |
| description | The identification of low-frequency antigen-specific CD4+ T cells is crucial for effective immunomonitoring across various diseases. However, this task still encounters experimental challenges necessitating the implementation of enrichment procedures. While existing antigen-specific expansion technologies predominantly concentrate on the enrichment of CD8+ T cells, advancements in methods targeting CD4+ T cells have been limited. In this study, we report a technique that harnesses antigen-presenting extracellular vesicles (EVs) for stimulation and expansion of antigen-specific CD4+ T cells. EVs are derived from a genetically modified HeLa cell line designed to emulate professional antigen-presenting cells (APCs) by expressing key costimulatory molecules CD80 and specific peptide–MHC-II complexes (pMHCs). Our results demonstrate the beneficial potent stimulatory capacity of EVs in activating both immortalized and isolated human CD4+ T cells from peripheral blood mononuclear cells (PBMCs). Our technique successfully expands low-frequency influenza-specific CD4+ T cells from healthy individuals. In summary, the elaborated methodology represents a streamlined and efficient approach for the detection and expansion of antigen-specific CD4+ T cells, presenting a valuable alternative to existing antigen-specific T-cell expansion protocols. |
| first_indexed | 2024-03-08T13:29:37Z |
| format | Article |
| id | doaj.art-a129dec8781a47c7902bb97ebee31679 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-03-08T13:29:37Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-a129dec8781a47c7902bb97ebee316792024-01-17T10:05:08ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852024-01-011110.3389/fbioe.2023.13416851341685Genetically engineered CD80–pMHC-harboring extracellular vesicles for antigen-specific CD4+ T-cell engagementIrina A. Ishina0Inna N. Kurbatskaia1Azad E. Mamedov2Elena I. Shramova3Sergey M. Deyev4Sergey M. Deyev5Sergey M. Deyev6Kamila S. Nurbaeva7Yury P. Rubtsov8Yury P. Rubtsov9Alexey A. Belogurov10Alexey A. Belogurov11Alexander G. Gabibov12Alexander G. Gabibov13Alexander G. Gabibov14Maria Y. Zakharova15Maria Y. Zakharova16Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, RussiaBiomarker Research Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, RussiaSechenov First Moscow State Medical University, Sechenov University, Moscow, RussiaV. A. Nasonova Research Institute of Rheumatology, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, RussiaN. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation (NN Blokhin NMRCO), Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, RussiaDepartment of Biological Chemistry, Evdokimov Moscow State University of Medicine and Dentistry, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, RussiaDepartment of Life Sciences, Higher School of Economics, Moscow, RussiaDepartment of Chemistry, Lomonosov Moscow State University, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, RussiaPirogov Russian National Research Medical University, Moscow, RussiaThe identification of low-frequency antigen-specific CD4+ T cells is crucial for effective immunomonitoring across various diseases. However, this task still encounters experimental challenges necessitating the implementation of enrichment procedures. While existing antigen-specific expansion technologies predominantly concentrate on the enrichment of CD8+ T cells, advancements in methods targeting CD4+ T cells have been limited. In this study, we report a technique that harnesses antigen-presenting extracellular vesicles (EVs) for stimulation and expansion of antigen-specific CD4+ T cells. EVs are derived from a genetically modified HeLa cell line designed to emulate professional antigen-presenting cells (APCs) by expressing key costimulatory molecules CD80 and specific peptide–MHC-II complexes (pMHCs). Our results demonstrate the beneficial potent stimulatory capacity of EVs in activating both immortalized and isolated human CD4+ T cells from peripheral blood mononuclear cells (PBMCs). Our technique successfully expands low-frequency influenza-specific CD4+ T cells from healthy individuals. In summary, the elaborated methodology represents a streamlined and efficient approach for the detection and expansion of antigen-specific CD4+ T cells, presenting a valuable alternative to existing antigen-specific T-cell expansion protocols.https://www.frontiersin.org/articles/10.3389/fbioe.2023.1341685/fullCD4+ T cellsextracellular vesiclesmajor histocompatibility complexcostimulatory moleculesantigen-specific expansion |
| spellingShingle | Irina A. Ishina Inna N. Kurbatskaia Azad E. Mamedov Elena I. Shramova Sergey M. Deyev Sergey M. Deyev Sergey M. Deyev Kamila S. Nurbaeva Yury P. Rubtsov Yury P. Rubtsov Alexey A. Belogurov Alexey A. Belogurov Alexander G. Gabibov Alexander G. Gabibov Alexander G. Gabibov Maria Y. Zakharova Maria Y. Zakharova Genetically engineered CD80–pMHC-harboring extracellular vesicles for antigen-specific CD4+ T-cell engagement Frontiers in Bioengineering and Biotechnology CD4+ T cells extracellular vesicles major histocompatibility complex costimulatory molecules antigen-specific expansion |
| title | Genetically engineered CD80–pMHC-harboring extracellular vesicles for antigen-specific CD4+ T-cell engagement |
| title_full | Genetically engineered CD80–pMHC-harboring extracellular vesicles for antigen-specific CD4+ T-cell engagement |
| title_fullStr | Genetically engineered CD80–pMHC-harboring extracellular vesicles for antigen-specific CD4+ T-cell engagement |
| title_full_unstemmed | Genetically engineered CD80–pMHC-harboring extracellular vesicles for antigen-specific CD4+ T-cell engagement |
| title_short | Genetically engineered CD80–pMHC-harboring extracellular vesicles for antigen-specific CD4+ T-cell engagement |
| title_sort | genetically engineered cd80 pmhc harboring extracellular vesicles for antigen specific cd4 t cell engagement |
| topic | CD4+ T cells extracellular vesicles major histocompatibility complex costimulatory molecules antigen-specific expansion |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1341685/full |
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