{"doi":"10.1101/2021.10.12.464035","title":"Brain endothelial antigen presentation detains CD8 <sup>+</sup> T cells at the blood-brain barrier leading to its breakdown","abstract":"Abstract Blood-brain barrier (BBB) breakdown and immune cell infiltration into the central nervous system (CNS) are early hallmarks of multiple sclerosis (MS). High numbers of CD8 + T cells are found in MS lesions and antigen (Ag)-presentation at the BBB was proposed to promote CD8 + T-cell entry into the CNS. Employing live cell imaging and primary mouse brain microvascular endothelial cells (pMBMECs) as in vitro model of the BBB and a mouse model of CNS autoimmunity, we here show that pMBMECs process and present antigens leading to effector CD8 + T-cell differentiation. Under physiological flow, endothelial Ag-presentation prohibited CD8 + T-cell crawling and diapedesis leading to pMBMEC apoptosis. Reduced motility of Ag-specific CD8 + T cells was also observed in CNS microvessels in neuroinflammation in vivo. Luminal MHC class I Ag-presentation at the BBB thus prohibits CD8 + T-cell entry into the CNS and rather triggers CD8 + T cell mediated focal BBB breakdown.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":227241,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9633,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":672926,"name":"Javier Pareja","orcid":"0000-0002-7563-1443","position":1,"is_corresponding":false},{"id":831583,"name":"Vivianne M. Schallenberg","orcid":null,"position":2,"is_corresponding":false},{"id":831584,"name":"Armelle Klopstein","orcid":null,"position":3,"is_corresponding":false},{"id":831073,"name":"Thomas Gruber","orcid":"0000-0001-5210-1995","position":4,"is_corresponding":false},{"id":831074,"name":"Nicolas Pagé","orcid":"0000-0002-5845-6831","position":5,"is_corresponding":false},{"id":831585,"name":"Elisa Kaba","orcid":null,"position":6,"is_corresponding":false},{"id":672927,"name":"Urban Deutsch","orcid":"0000-0003-4265-6262","position":7,"is_corresponding":false},{"id":256585,"name":"Aaron J. Johnson","orcid":"0000-0002-7921-484X","position":8,"is_corresponding":false},{"id":831075,"name":"Mirjam Schenk","orcid":"0000-0002-1637-0730","position":9,"is_corresponding":false},{"id":644577,"name":"Doron Merkler","orcid":"0000-0002-0247-2007","position":10,"is_corresponding":false},{"id":279353,"name":"Britta Engelhardt","orcid":"0000-0003-3059-9846","position":11,"is_corresponding":false},{"id":831072,"name":"Sidar Aydin","orcid":"0000-0001-7791-7931","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:54:42.179886Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}