DNA methylation profiling identifies TBKBP1 as potent amplifier of cytotoxic activity in CMV-specific human CD8+ T cells. Yu, Z., Sasidharan-Nair, V., Bonifacius, A., Khan, F., Buchta, T., Beckstette, M., Niemz, J., Hilgendorf, P., Pietzsch, B., Mausberg, P., Keller, A., Falk, C., Busch, D., Brinkmann, M. M., Schober, K., Cicin-Sain, L., Müller, F., Eiz-Vesper, B., Floess, S., & Huehn, J. bioRxiv, Cold Spring Harbor Laboratory, 2023. ![DNA methylation profiling identifies TBKBP1 as potent amplifier of cytotoxic activity in CMV-specific human CD8+ T cells [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Epigenetic mechanisms stabilize gene expression patterns during CD8+ T cell differentiation. However, although adoptive transfer of virus-specific T cells is clinically applied to reduce the risk of virus infection or reactivation in immunocompromised individuals, the DNA methylation pattern of virus-specific CD8+ T cells is largely unknown. Hence, we here performed whole-genome bisulfite sequencing of cytomegalovirus-specific human CD8+ T cells and found that they display a unique DNA methylation pattern consisting of 79 differentially methylated regions when compared to bulk memory CD8+ T cells. Among them was TBKBP1, coding for TBK-binding protein 1 that can interact with TANK-binding kinase 1 (TBK1) and mediate pro-inflammatory responses in innate immune cells downstream of intracellular virus sensing. Since TBKBP1 has not yet been reported in T cells, we aimed to unravel its role in virus-specific CD8+ T cells. TBKBP1 demethylation in terminal effector CD8+ T cells correlated with TBKBP1 expression and was stable upon long-term in vitro culture. TBKBP1 overexpression resulted in enhanced TBK1 phosphorylation upon stimulation of CD8+ T cells and significantly improved their virus neutralization capacity. Collectively, our data demonstrate that TBKBP1 modulates virus-specific CD8+ T cell responses and could be exploited as therapeutic target to improve adoptive T cell therapies.Competing Interest StatementThe authors have declared no competing interest.
@article {Yu2023.11.06.565829,
author = {Zheng Yu and Varun Sasidharan-Nair and Agnes Bonifacius and Fawad Khan and Thalea Buchta and Michael Beckstette and Jana Niemz and Philipp Hilgendorf and Beate Pietzsch and Philip Mausberg and Andreas Keller and Christine Falk and Dirk Busch and Melanie M. Brinkmann and Kilian Schober and Luka Cicin-Sain and Fabian M{\"u}ller and Britta Eiz-Vesper and Stefan Floess and Jochen Huehn},
title = {DNA methylation profiling identifies TBKBP1 as potent amplifier of cytotoxic activity in CMV-specific human CD8+ T cells},
elocation-id = {2023.11.06.565829},
year = {2023},
doi = {10.1101/2023.11.06.565829},
publisher = {Cold Spring Harbor Laboratory},
abstract = {Epigenetic mechanisms stabilize gene expression patterns during CD8+ T cell differentiation. However, although adoptive transfer of virus-specific T cells is clinically applied to reduce the risk of virus infection or reactivation in immunocompromised individuals, the DNA methylation pattern of virus-specific CD8+ T cells is largely unknown. Hence, we here performed whole-genome bisulfite sequencing of cytomegalovirus-specific human CD8+ T cells and found that they display a unique DNA methylation pattern consisting of 79 differentially methylated regions when compared to bulk memory CD8+ T cells. Among them was TBKBP1, coding for TBK-binding protein 1 that can interact with TANK-binding kinase 1 (TBK1) and mediate pro-inflammatory responses in innate immune cells downstream of intracellular virus sensing. Since TBKBP1 has not yet been reported in T cells, we aimed to unravel its role in virus-specific CD8+ T cells. TBKBP1 demethylation in terminal effector CD8+ T cells correlated with TBKBP1 expression and was stable upon long-term in vitro culture. TBKBP1 overexpression resulted in enhanced TBK1 phosphorylation upon stimulation of CD8+ T cells and significantly improved their virus neutralization capacity. Collectively, our data demonstrate that TBKBP1 modulates virus-specific CD8+ T cell responses and could be exploited as therapeutic target to improve adoptive T cell therapies.Competing Interest StatementThe authors have declared no competing interest.},
URL = {https://www.biorxiv.org/content/early/2023/11/06/2023.11.06.565829},
eprint = {https://www.biorxiv.org/content/early/2023/11/06/2023.11.06.565829.full.pdf},
journal = {bioRxiv}
}
Downloads: 0
{"_id":"8dBFzgQGo2r2hFSrE","bibbaseid":"yu-sasidharannair-bonifacius-khan-buchta-beckstette-niemz-hilgendorf-etal-dnamethylationprofilingidentifiestbkbp1aspotentamplifierofcytotoxicactivityincmvspecifichumancd8tcells-2023","author_short":["Yu, Z.","Sasidharan-Nair, V.","Bonifacius, A.","Khan, F.","Buchta, T.","Beckstette, M.","Niemz, J.","Hilgendorf, P.","Pietzsch, B.","Mausberg, P.","Keller, A.","Falk, C.","Busch, D.","Brinkmann, M. M.","Schober, K.","Cicin-Sain, L.","Müller, F.","Eiz-Vesper, B.","Floess, S.","Huehn, J."],"bibdata":{"bibtype":"article","type":"article","author":[{"firstnames":["Zheng"],"propositions":[],"lastnames":["Yu"],"suffixes":[]},{"firstnames":["Varun"],"propositions":[],"lastnames":["Sasidharan-Nair"],"suffixes":[]},{"firstnames":["Agnes"],"propositions":[],"lastnames":["Bonifacius"],"suffixes":[]},{"firstnames":["Fawad"],"propositions":[],"lastnames":["Khan"],"suffixes":[]},{"firstnames":["Thalea"],"propositions":[],"lastnames":["Buchta"],"suffixes":[]},{"firstnames":["Michael"],"propositions":[],"lastnames":["Beckstette"],"suffixes":[]},{"firstnames":["Jana"],"propositions":[],"lastnames":["Niemz"],"suffixes":[]},{"firstnames":["Philipp"],"propositions":[],"lastnames":["Hilgendorf"],"suffixes":[]},{"firstnames":["Beate"],"propositions":[],"lastnames":["Pietzsch"],"suffixes":[]},{"firstnames":["Philip"],"propositions":[],"lastnames":["Mausberg"],"suffixes":[]},{"firstnames":["Andreas"],"propositions":[],"lastnames":["Keller"],"suffixes":[]},{"firstnames":["Christine"],"propositions":[],"lastnames":["Falk"],"suffixes":[]},{"firstnames":["Dirk"],"propositions":[],"lastnames":["Busch"],"suffixes":[]},{"firstnames":["Melanie","M."],"propositions":[],"lastnames":["Brinkmann"],"suffixes":[]},{"firstnames":["Kilian"],"propositions":[],"lastnames":["Schober"],"suffixes":[]},{"firstnames":["Luka"],"propositions":[],"lastnames":["Cicin-Sain"],"suffixes":[]},{"firstnames":["Fabian"],"propositions":[],"lastnames":["Müller"],"suffixes":[]},{"firstnames":["Britta"],"propositions":[],"lastnames":["Eiz-Vesper"],"suffixes":[]},{"firstnames":["Stefan"],"propositions":[],"lastnames":["Floess"],"suffixes":[]},{"firstnames":["Jochen"],"propositions":[],"lastnames":["Huehn"],"suffixes":[]}],"title":"DNA methylation profiling identifies TBKBP1 as potent amplifier of cytotoxic activity in CMV-specific human CD8+ T cells","elocation-id":"2023.11.06.565829","year":"2023","doi":"10.1101/2023.11.06.565829","publisher":"Cold Spring Harbor Laboratory","abstract":"Epigenetic mechanisms stabilize gene expression patterns during CD8+ T cell differentiation. However, although adoptive transfer of virus-specific T cells is clinically applied to reduce the risk of virus infection or reactivation in immunocompromised individuals, the DNA methylation pattern of virus-specific CD8+ T cells is largely unknown. Hence, we here performed whole-genome bisulfite sequencing of cytomegalovirus-specific human CD8+ T cells and found that they display a unique DNA methylation pattern consisting of 79 differentially methylated regions when compared to bulk memory CD8+ T cells. Among them was TBKBP1, coding for TBK-binding protein 1 that can interact with TANK-binding kinase 1 (TBK1) and mediate pro-inflammatory responses in innate immune cells downstream of intracellular virus sensing. Since TBKBP1 has not yet been reported in T cells, we aimed to unravel its role in virus-specific CD8+ T cells. TBKBP1 demethylation in terminal effector CD8+ T cells correlated with TBKBP1 expression and was stable upon long-term in vitro culture. TBKBP1 overexpression resulted in enhanced TBK1 phosphorylation upon stimulation of CD8+ T cells and significantly improved their virus neutralization capacity. Collectively, our data demonstrate that TBKBP1 modulates virus-specific CD8+ T cell responses and could be exploited as therapeutic target to improve adoptive T cell therapies.Competing Interest StatementThe authors have declared no competing interest.","url":"https://www.biorxiv.org/content/early/2023/11/06/2023.11.06.565829","eprint":"https://www.biorxiv.org/content/early/2023/11/06/2023.11.06.565829.full.pdf","journal":"bioRxiv","bibtex":"@article {Yu2023.11.06.565829,\n\tauthor = {Zheng Yu and Varun Sasidharan-Nair and Agnes Bonifacius and Fawad Khan and Thalea Buchta and Michael Beckstette and Jana Niemz and Philipp Hilgendorf and Beate Pietzsch and Philip Mausberg and Andreas Keller and Christine Falk and Dirk Busch and Melanie M. Brinkmann and Kilian Schober and Luka Cicin-Sain and Fabian M{\\\"u}ller and Britta Eiz-Vesper and Stefan Floess and Jochen Huehn},\n\ttitle = {DNA methylation profiling identifies TBKBP1 as potent amplifier of cytotoxic activity in CMV-specific human CD8+ T cells},\n\telocation-id = {2023.11.06.565829},\n\tyear = {2023},\n\tdoi = {10.1101/2023.11.06.565829},\n\tpublisher = {Cold Spring Harbor Laboratory},\n\tabstract = {Epigenetic mechanisms stabilize gene expression patterns during CD8+ T cell differentiation. However, although adoptive transfer of virus-specific T cells is clinically applied to reduce the risk of virus infection or reactivation in immunocompromised individuals, the DNA methylation pattern of virus-specific CD8+ T cells is largely unknown. Hence, we here performed whole-genome bisulfite sequencing of cytomegalovirus-specific human CD8+ T cells and found that they display a unique DNA methylation pattern consisting of 79 differentially methylated regions when compared to bulk memory CD8+ T cells. Among them was TBKBP1, coding for TBK-binding protein 1 that can interact with TANK-binding kinase 1 (TBK1) and mediate pro-inflammatory responses in innate immune cells downstream of intracellular virus sensing. Since TBKBP1 has not yet been reported in T cells, we aimed to unravel its role in virus-specific CD8+ T cells. TBKBP1 demethylation in terminal effector CD8+ T cells correlated with TBKBP1 expression and was stable upon long-term in vitro culture. TBKBP1 overexpression resulted in enhanced TBK1 phosphorylation upon stimulation of CD8+ T cells and significantly improved their virus neutralization capacity. Collectively, our data demonstrate that TBKBP1 modulates virus-specific CD8+ T cell responses and could be exploited as therapeutic target to improve adoptive T cell therapies.Competing Interest StatementThe authors have declared no competing interest.},\n\tURL = {https://www.biorxiv.org/content/early/2023/11/06/2023.11.06.565829},\n\teprint = {https://www.biorxiv.org/content/early/2023/11/06/2023.11.06.565829.full.pdf},\n\tjournal = {bioRxiv}\n}\n\n","author_short":["Yu, Z.","Sasidharan-Nair, V.","Bonifacius, A.","Khan, F.","Buchta, T.","Beckstette, M.","Niemz, J.","Hilgendorf, P.","Pietzsch, B.","Mausberg, P.","Keller, A.","Falk, C.","Busch, D.","Brinkmann, M. M.","Schober, K.","Cicin-Sain, L.","Müller, F.","Eiz-Vesper, B.","Floess, S.","Huehn, J."],"key":"Yu2023.11.06.565829","id":"Yu2023.11.06.565829","bibbaseid":"yu-sasidharannair-bonifacius-khan-buchta-beckstette-niemz-hilgendorf-etal-dnamethylationprofilingidentifiestbkbp1aspotentamplifierofcytotoxicactivityincmvspecifichumancd8tcells-2023","role":"author","urls":{"Paper":"https://www.biorxiv.org/content/early/2023/11/06/2023.11.06.565829"},"metadata":{"authorlinks":{}},"html":""},"bibtype":"article","biburl":"https://www.ccb.uni-saarland.de/wp-content/uploads/2024/05/preprints.bib_.txt","dataSources":["3GiWHWJ88tGn5tcej","G4LygabMCr4Wh2h3G"],"keywords":[],"search_terms":["dna","methylation","profiling","identifies","tbkbp1","potent","amplifier","cytotoxic","activity","cmv","specific","human","cd8","cells","yu","sasidharan-nair","bonifacius","khan","buchta","beckstette","niemz","hilgendorf","pietzsch","mausberg","keller","falk","busch","brinkmann","schober","cicin-sain","müller","eiz-vesper","floess","huehn"],"title":"DNA methylation profiling identifies TBKBP1 as potent amplifier of cytotoxic activity in CMV-specific human CD8+ T cells","year":2023}