{"id":{"repo_id":"cambridge","oai_identifier":"oai:www.repository.cam.ac.uk:1810/336771"},"canonical_url":"https://search.dev.ndltd.org/etd/cambridge/oai:www.repository.cam.ac.uk:1810/336771","repository":{"repo_id":"cambridge","name":"Cambridge University","base_url":"https://api.repository.cam.ac.uk/server/oai/request"},"display":{"title":"The RNA-Binding protein PTBP1 plays a role in the activation of mouse CD8 T cells","abstract":"CD8 T cells play a pivotal role in immune responses against intracellular pathogens, including viruses and bacteria, and in tumour surveillance. After encountering an antigen, CD8 T cells undergo cell growth, clonal expansion, and acquisition of effector functions. These steps are a result of controlled gene expression changes dependent on transcriptional and post- transcriptional mechanisms. These processes are tightly regulated, but little is known about the mechanisms through which these processes are integrated. RNA-binding proteins play a pivotal role in controlling and regulating these processes. Here we show how the RNA-binding protein PTBP1 is dispensable for T cell development but has an essential role in regulating CD8 T cell activation, proliferation, and production of effector molecules. To investigate the roles of PTBP1 in CD8 T cells we generated a mouse model which conditionally deletes Ptbp1 in mature T cells. We found that PTBP1 has an essential role in regulating early events in CD8T cell activation resulting in the production of the effector molecules IL-2 and TNFa. It is also required for optimal proliferation and survival of clonally expanding CD8 T cells. PTBP1 controls a program of Alternative Splicing of many genes. One of these, the catalytic subunit of Calcineurin Ab and Ag may be linked to translocation of c-Fos, NFATc2 and NFATc3 in the nucleus of T cells. These findings reveal a crucial role for PTBP1 in regulating post-transcriptional regulation of genes involved in CD8 T cell activation and effector functions.","abstract_html":"CD8 T cells play a pivotal role in immune responses against intracellular pathogens, including viruses and bacteria, and in tumour surveillance. After encountering an antigen, CD8 T cells undergo cell growth, clonal expansion, and acquisition of effector functions. These steps are a result of controlled gene expression changes dependent on transcriptional and post- transcriptional mechanisms. These processes are tightly regulated, but little is known about the mechanisms through which these processes are integrated. RNA-binding proteins play a pivotal role in controlling and regulating these processes. Here we show how the RNA-binding protein PTBP1 is dispensable for T cell development but has an essential role in regulating CD8 T cell activation, proliferation, and production of effector molecules. To investigate the roles of PTBP1 in CD8 T cells we generated a mouse model which conditionally deletes Ptbp1 in mature T cells. We found that PTBP1 has an essential role in regulating early events in CD8T cell activation resulting in the production of the effector molecules IL-2 and TNFa. It is also required for optimal proliferation and survival of clonally expanding CD8 T cells. PTBP1 controls a program of Alternative Splicing of many genes. One of these, the catalytic subunit of Calcineurin Ab and Ag may be linked to translocation of c-Fos, NFATc2 and NFATc3 in the nucleus of T cells. These findings reveal a crucial role for PTBP1 in regulating post-transcriptional regulation of genes involved in CD8 T cell activation and effector functions.","abstract_has_math":false,"creators":["D'Angeli, Vanessa"],"institution":"University of Cambridge","degree_name":"Doctor of Philosophy (PhD)","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Turner, Martin"],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-01-30","date_published":"2022-01-30","updated_at":"2026-07-22T22:24:17Z","subjects":["CD8 T cells","RNA Binding Proteins","Gene Regulation","Cellular activation"],"languages":["eng"],"rights":[],"rights_urls":["https://www.rioxx.net/licenses/all-rights-reserved/"],"identifier_entries":[]},"links":{"outbound_url":"https://doi.org/10.17863/CAM.84189","outbound_label":"DOI","outbound_source":"dc:identifier.doi"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Turner, Martin"]},{"key":"dc:creator","label":"Author","values":["D'Angeli, Vanessa"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2022-01-30"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Cambridge"]},{"key":"dc:relation.isreferencedby.uri","label":"Dc Relation Isreferencedby URI","values":["https://www.repository.cam.ac.uk/handle/1810/336771"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["CD8 T cells","RNA Binding Proteins","Gene Regulation","Cellular activation"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["https://www.rioxx.net/licenses/all-rights-reserved/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.doi","label":"DOI","values":["10.17863/CAM.84189"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/94190ab2-7ad3-40cb-8ecd-ea7dc3513f41/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["CD8 T cells play a pivotal role in immune responses against intracellular pathogens, including viruses and bacteria, and in tumour surveillance. After encountering an antigen, CD8 T cells undergo cell growth, clonal expansion, and acquisition of effector functions. These steps are a result of controlled gene expression changes dependent on transcriptional and post- transcriptional mechanisms. These processes are tightly regulated, but little is known about the mechanisms through which these processes are integrated. RNA-binding proteins play a pivotal role in controlling and regulating these processes. Here we show how the RNA-binding protein PTBP1 is dispensable for T cell development but has an essential role in regulating CD8 T cell activation, proliferation, and production of effector molecules. To investigate the roles of PTBP1 in CD8 T cells we generated a mouse model which conditionally deletes Ptbp1 in mature T cells. We found that PTBP1 has an essential role in regulating early events in CD8T cell activation resulting in the production of the effector molecules IL-2 and TNFa. It is also required for optimal proliferation and survival of clonally expanding CD8 T cells. PTBP1 controls a program of Alternative Splicing of many genes. One of these, the catalytic subunit of Calcineurin Ab and Ag may be linked to translocation of c-Fos, NFATc2 and NFATc3 in the nucleus of T cells. 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These processes are tightly regulated, but little is known about the mechanisms through which these processes are integrated. RNA-binding proteins play a pivotal role in controlling and regulating these processes. Here we show how the RNA-binding protein PTBP1 is dispensable for T cell development but has an essential role in regulating CD8 T cell activation, proliferation, and production of effector molecules. To investigate the roles of PTBP1 in CD8 T cells we generated a mouse model which conditionally deletes Ptbp1 in mature T cells. We found that PTBP1 has an essential role in regulating early events in CD8T cell activation resulting in the production of the effector molecules IL-2 and TNFa. It is also required for optimal proliferation and survival of clonally expanding CD8 T cells. PTBP1 controls a program of Alternative Splicing of many genes. One of these, the catalytic subunit of Calcineurin Ab and Ag may be linked to translocation of c-Fos, NFATc2 and NFATc3 in the nucleus of T cells. These findings reveal a crucial role for PTBP1 in regulating post-transcriptional regulation of genes involved in CD8 T cell activation and effector functions."],"dc:format.checksum.md5":["8b41a838cb8b4d205d854d93f66c9959"],"dc:identifier.doi":["10.17863/CAM.84189"],"dc:identifier.uri":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/94190ab2-7ad3-40cb-8ecd-ea7dc3513f41/download"],"dc:language":["eng"],"dc:publisher.institution":["University of Cambridge"],"dc:relation.isreferencedby.uri":["https://www.repository.cam.ac.uk/handle/1810/336771"],"dc:rights":["https://www.rioxx.net/licenses/all-rights-reserved/"],"dc:subject":["CD8 T cells","RNA Binding Proteins","Gene Regulation","Cellular activation"],"dc:title":["The RNA-Binding protein PTBP1 plays a role in the activation of mouse CD8 T cells"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["Doctoral"],"dc:type.qualificationname":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-22T22:24:17Z"}