Polymerised superparamagnetic antigen presenting cell lymphocyte capture for enriching tumour reactive T-cells and neoantigen identification
Abstract Ultrasensitive antigen recognition between T lymphocytes and cognate targets via immunological synapse (IS) formation enables live cell-based antigen-specific T cell detection. However, unpredictable antigen processing and major histocompatibility complex (MHC) turnover limit specificity. H...
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Nature Portfolio
2025-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60321-3 |
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| author | Chung-Yao Hsu Po-Cheng Tsai Jung-Chen Lin Chen-Hsueh Pai Yun-Jui Teng Bing-Yu Yao Cheng-Yin Fei Gwo Harn Max Shiau Leon CW Lin Sean Lo Hung-Chih Yang Che-Ming Jack Hu |
| author_facet | Chung-Yao Hsu Po-Cheng Tsai Jung-Chen Lin Chen-Hsueh Pai Yun-Jui Teng Bing-Yu Yao Cheng-Yin Fei Gwo Harn Max Shiau Leon CW Lin Sean Lo Hung-Chih Yang Che-Ming Jack Hu |
| author_sort | Chung-Yao Hsu |
| collection | DOAJ |
| description | Abstract Ultrasensitive antigen recognition between T lymphocytes and cognate targets via immunological synapse (IS) formation enables live cell-based antigen-specific T cell detection. However, unpredictable antigen processing and major histocompatibility complex (MHC) turnover limit specificity. Here, intracellularly polymerized antigen-presenting cells (pAPCs) are developed for modular, persistent antigen display via kinetically driven loading. Although inanimate, pAPCs mimic cellular interactions, inducing IS hallmarks such as supramolecular activation cluster formation, cytoskeletal contraction, and trogocytosis. Incorporation of superparamagnetic nanoparticles allows label-free magnetic isolation of antigen-specific T cells, surpassing MHC-conjugated beads in sensitivity and specificity. In tumor-bearing hosts, pAPCs enrich tumor-reactive lymphocytes, enhancing adoptive T cell therapy and neoantigen-specific T cell identification. Additionally, pAPCs from engineered cells expressing monovalent human MHC enrich virus- and tumor-specific CD8 T cells from human peripheral blood mononuclear cells and human leukocyte antigen-transgenic mice, demonstrating the potential of this cell–gel hybrid platform for precise antigen-specific T cell capture. |
| format | Article |
| id | doaj-art-034e30c2c4554736b63334400d68ed40 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-034e30c2c4554736b63334400d68ed402025-08-20T02:30:42ZengNature PortfolioNature Communications2041-17232025-06-0116111610.1038/s41467-025-60321-3Polymerised superparamagnetic antigen presenting cell lymphocyte capture for enriching tumour reactive T-cells and neoantigen identificationChung-Yao Hsu0Po-Cheng Tsai1Jung-Chen Lin2Chen-Hsueh Pai3Yun-Jui Teng4Bing-Yu Yao5Cheng-Yin Fei6Gwo Harn Max Shiau7Leon CW Lin8Sean Lo9Hung-Chih Yang10Che-Ming Jack Hu11Taiwan International Graduate Student Program, National Yang Ming Chao Tung University and Academia SinicaTaiwan International Graduate Student Program, National Yang Ming Chao Tung University and Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaDepartment of Biochemical Science and Technology, College of Life Science, National Taiwan UniversityInstitute of Biomedical Sciences, Academia SinicaTaiwan International Graduate Student Program, National Yang Ming Chao Tung University and Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaGraduate Institute of Microbiology, College of Medicine, National Taiwan UniversityTaiwan International Graduate Student Program, National Yang Ming Chao Tung University and Academia SinicaAbstract Ultrasensitive antigen recognition between T lymphocytes and cognate targets via immunological synapse (IS) formation enables live cell-based antigen-specific T cell detection. However, unpredictable antigen processing and major histocompatibility complex (MHC) turnover limit specificity. Here, intracellularly polymerized antigen-presenting cells (pAPCs) are developed for modular, persistent antigen display via kinetically driven loading. Although inanimate, pAPCs mimic cellular interactions, inducing IS hallmarks such as supramolecular activation cluster formation, cytoskeletal contraction, and trogocytosis. Incorporation of superparamagnetic nanoparticles allows label-free magnetic isolation of antigen-specific T cells, surpassing MHC-conjugated beads in sensitivity and specificity. In tumor-bearing hosts, pAPCs enrich tumor-reactive lymphocytes, enhancing adoptive T cell therapy and neoantigen-specific T cell identification. Additionally, pAPCs from engineered cells expressing monovalent human MHC enrich virus- and tumor-specific CD8 T cells from human peripheral blood mononuclear cells and human leukocyte antigen-transgenic mice, demonstrating the potential of this cell–gel hybrid platform for precise antigen-specific T cell capture.https://doi.org/10.1038/s41467-025-60321-3 |
| spellingShingle | Chung-Yao Hsu Po-Cheng Tsai Jung-Chen Lin Chen-Hsueh Pai Yun-Jui Teng Bing-Yu Yao Cheng-Yin Fei Gwo Harn Max Shiau Leon CW Lin Sean Lo Hung-Chih Yang Che-Ming Jack Hu Polymerised superparamagnetic antigen presenting cell lymphocyte capture for enriching tumour reactive T-cells and neoantigen identification Nature Communications |
| title | Polymerised superparamagnetic antigen presenting cell lymphocyte capture for enriching tumour reactive T-cells and neoantigen identification |
| title_full | Polymerised superparamagnetic antigen presenting cell lymphocyte capture for enriching tumour reactive T-cells and neoantigen identification |
| title_fullStr | Polymerised superparamagnetic antigen presenting cell lymphocyte capture for enriching tumour reactive T-cells and neoantigen identification |
| title_full_unstemmed | Polymerised superparamagnetic antigen presenting cell lymphocyte capture for enriching tumour reactive T-cells and neoantigen identification |
| title_short | Polymerised superparamagnetic antigen presenting cell lymphocyte capture for enriching tumour reactive T-cells and neoantigen identification |
| title_sort | polymerised superparamagnetic antigen presenting cell lymphocyte capture for enriching tumour reactive t cells and neoantigen identification |
| url | https://doi.org/10.1038/s41467-025-60321-3 |
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