{"id":"https://openalex.org/W2921574434","doi":"https://doi.org/10.1101/574608","title":"T Cell Receptor Immunotherapy Drives Human Immunodeficiency Virus Evolution in Humanized Mice","display_name":"T Cell Receptor Immunotherapy Drives Human Immunodeficiency Virus Evolution in Humanized Mice","publication_year":2019,"publication_date":"2019-03-12","ids":{"openalex":"https://openalex.org/W2921574434","doi":"https://doi.org/10.1101/574608","mag":"2921574434"},"language":"en","primary_location":{"id":"doi:10.1101/574608","doi":"https://doi.org/10.1101/574608","is_oa":true,"landing_page_url":"https://doi.org/10.1101/574608","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2019/03/12/574608.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2019/03/12/574608.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5111021846","display_name":"Alok V. Joglekar","orcid":"https://orcid.org/0000-0001-7554-7447","observed_orcids":["https://orcid.org/0000-0001-7554-7447"]},"institutions":[{"id":"https://openalex.org/I122411786","display_name":"California Institute of Technology","ror":"https://ror.org/05dxps055","country_code":"US","type":"education","lineage":["https://openalex.org/I122411786"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Alok V. Joglekar","raw_affiliation_strings":["Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA"],"raw_orcid":"https://orcid.org/0000-0001-7554-7447","affiliations":[{"raw_affiliation_string":"Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA","institution_ids":["https://openalex.org/I122411786"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5047732590","display_name":"M Swift","orcid":"https://orcid.org/0000-0001-9610-0687","observed_orcids":["https://orcid.org/0000-0001-9610-0687"]},"institutions":[{"id":"https://openalex.org/I122411786","display_name":"California Institute of Technology","ror":"https://ror.org/05dxps055","country_code":"US","type":"education","lineage":["https://openalex.org/I122411786"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Margaret Swift","raw_affiliation_strings":["Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA","institution_ids":["https://openalex.org/I122411786"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5026206729","display_name":"Michael Troy Leonard","orcid":"https://orcid.org/0000-0001-9084-2647","observed_orcids":["https://orcid.org/0000-0001-9084-2647"]},"institutions":[{"id":"https://openalex.org/I122411786","display_name":"California Institute of Technology","ror":"https://ror.org/05dxps055","country_code":"US","type":"education","lineage":["https://openalex.org/I122411786"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Michael T. Leonard","raw_affiliation_strings":["Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA","institution_ids":["https://openalex.org/I122411786"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5043690934","display_name":"John David Jeppson","orcid":"https://orcid.org/0000-0002-9669-0813","observed_orcids":["https://orcid.org/0000-0002-9669-0813"]},"institutions":[{"id":"https://openalex.org/I122411786","display_name":"California Institute of Technology","ror":"https://ror.org/05dxps055","country_code":"US","type":"education","lineage":["https://openalex.org/I122411786"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"John D. Jeppson","raw_affiliation_strings":["Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA","institution_ids":["https://openalex.org/I122411786"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5028356747","display_name":"Salemiz Sandoval","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I122411786","display_name":"California Institute of Technology","ror":"https://ror.org/05dxps055","country_code":"US","type":"education","lineage":["https://openalex.org/I122411786"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Salemiz Sandoval","raw_affiliation_strings":["Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA","institution_ids":["https://openalex.org/I122411786"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5042763205","display_name":"David Baltimore","orcid":"https://orcid.org/0000-0001-8723-8190","observed_orcids":["https://orcid.org/0000-0001-8723-8190"]},"institutions":[{"id":"https://openalex.org/I122411786","display_name":"California Institute of Technology","ror":"https://ror.org/05dxps055","country_code":"US","type":"education","lineage":["https://openalex.org/I122411786"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"David Baltimore","raw_affiliation_strings":["Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA","institution_ids":["https://openalex.org/I122411786"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5042763205","https://openalex.org/A5111021846"],"corresponding_institution_ids":["https://openalex.org/I122411786"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10112","display_name":"HIV Research and Treatment","score":0.9984999895095825,"subfield":{"id":"https://openalex.org/subfields/2406","display_name":"Virology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10112","display_name":"HIV Research and Treatment","score":0.9984999895095825,"subfield":{"id":"https://openalex.org/subfields/2406","display_name":"Virology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10613","display_name":"Virus-based gene therapy research","score":0.0005000000237487257,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11491","display_name":"CAR-T cell therapy research","score":0.00019999999494757503,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/hiv","display_name":"HIV","score":0.7699999809265137},{"id":"https://openalex.org/keywords/hiv-controllers","display_name":"HIV controllers","score":0.675000011920929},{"id":"https://openalex.org/keywords/hla-b-2705","display_name":"HLA-B*2705","score":0.8550000190734863},{"id":"https://openalex.org/keywords/viral-evolution","display_name":"viral evolution","score":0.6570000052452087},{"id":"https://openalex.org/keywords/cd8-t-cell-responses","display_name":"CD8+ T cell responses","score":0.7179999947547913},{"id":"https://openalex.org/keywords/hematopoietic-stem-and-progenitor-cells","display_name":"hematopoietic stem and progenitor cells","score":0.8270000219345093},{"id":"https://openalex.org/keywords/humanized-mouse-model","display_name":"humanized mice","score":0.746999979019165},{"id":"https://openalex.org/keywords/viral-escape-mutations","display_name":"viral escape mutations","score":0.6190000176429749},{"id":"https://openalex.org/keywords/cd4-t-cell-reconstitution","display_name":"CD4+ T cell recovery","score":0.6990000009536743}],"concepts":[{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.6478760838508606},{"id":"https://openalex.org/C2776156784","wikidata":"https://www.wikidata.org/wiki/Q3491954","display_name":"Humanized mouse","level":3,"score":0.6400318145751953},{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.6313918828964233},{"id":"https://openalex.org/C19317047","wikidata":"https://www.wikidata.org/wiki/Q412037","display_name":"T-cell receptor","level":4,"score":0.5802891254425049},{"id":"https://openalex.org/C167672396","wikidata":"https://www.wikidata.org/wiki/Q417800","display_name":"CD8","level":3,"score":0.5716449022293091},{"id":"https://openalex.org/C159047783","wikidata":"https://www.wikidata.org/wiki/Q7215","display_name":"Virology","level":1,"score":0.55315101146698},{"id":"https://openalex.org/C195616568","wikidata":"https://www.wikidata.org/wiki/Q128711","display_name":"Epitope","level":3,"score":0.5346637964248657},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.5261504054069519},{"id":"https://openalex.org/C2778086970","wikidata":"https://www.wikidata.org/wiki/Q514525","display_name":"Hematopoietic stem cell","level":4,"score":0.46891602873802185},{"id":"https://openalex.org/C2776090121","wikidata":"https://www.wikidata.org/wiki/Q193529","display_name":"T cell","level":3,"score":0.4546029269695282},{"id":"https://openalex.org/C154317977","wikidata":"https://www.wikidata.org/wiki/Q376266","display_name":"Cytotoxic T cell","level":3,"score":0.4209940433502197},{"id":"https://openalex.org/C188280979","wikidata":"https://www.wikidata.org/wiki/Q911125","display_name":"Human leukocyte antigen","level":3,"score":0.4182438850402832},{"id":"https://openalex.org/C28328180","wikidata":"https://www.wikidata.org/wiki/Q48196","display_name":"Stem cell","level":2,"score":0.4048860967159271},{"id":"https://openalex.org/C109159458","wikidata":"https://www.wikidata.org/wiki/Q919283","display_name":"Haematopoiesis","level":3,"score":0.38966333866119385},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.25388002395629883},{"id":"https://openalex.org/C147483822","wikidata":"https://www.wikidata.org/wiki/Q103537","display_name":"Antigen","level":2,"score":0.2222089171409607},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.1882035732269287},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.09380576014518738},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.0}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.1101/574608","doi":"https://doi.org/10.1101/574608","is_oa":true,"landing_page_url":"https://doi.org/10.1101/574608","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2019/03/12/574608.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},{"id":"pmh:oai:authors.library.caltech.edu:93721","doi":null,"is_oa":false,"landing_page_url":"https://resolver.caltech.edu/CaltechAUTHORS:20190312-085351129","pdf_url":null,"source":{"id":"https://openalex.org/S4306402161","display_name":"CaltechAUTHORS (California Institute of Technology)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I122411786","host_organization_name":"California Institute of Technology","host_organization_lineage":["https://openalex.org/I122411786"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"Report or Paper"}],"best_oa_location":{"id":"doi:10.1101/574608","doi":"https://doi.org/10.1101/574608","is_oa":true,"landing_page_url":"https://doi.org/10.1101/574608","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2019/03/12/574608.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9763000011444092}],"sustainable_development_goals_aurora":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.7699999809265137}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320309398","display_name":"California Institute of Technology","ror":"https://ror.org/05dxps055"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2921574434.pdf","grobid_xml":"https://content.openalex.org/works/W2921574434.grobid-xml"},"referenced_works_count":42,"referenced_works":["https://openalex.org/W1898340442","https://openalex.org/W1993328343","https://openalex.org/W2003051762","https://openalex.org/W2008284182","https://openalex.org/W2016364569","https://openalex.org/W2027501809","https://openalex.org/W2030445837","https://openalex.org/W2030677933","https://openalex.org/W2033839702","https://openalex.org/W2042718212","https://openalex.org/W2044587042","https://openalex.org/W2045551237","https://openalex.org/W2073001017","https://openalex.org/W2080720232","https://openalex.org/W2097705840","https://openalex.org/W2103314023","https://openalex.org/W2112445435","https://openalex.org/W2121315503","https://openalex.org/W2123063882","https://openalex.org/W2123906548","https://openalex.org/W2128446740","https://openalex.org/W2129174937","https://openalex.org/W2132262344","https://openalex.org/W2138579509","https://openalex.org/W2143430982","https://openalex.org/W2148323928","https://openalex.org/W2149608750","https://openalex.org/W2155721915","https://openalex.org/W2160110394","https://openalex.org/W2160822369","https://openalex.org/W2166378435","https://openalex.org/W2266944971","https://openalex.org/W2394566891","https://openalex.org/W2595661323","https://openalex.org/W2620965804","https://openalex.org/W2762583307","https://openalex.org/W2779290696","https://openalex.org/W2787064560","https://openalex.org/W2789820203","https://openalex.org/W2800845257","https://openalex.org/W2911644242","https://openalex.org/W2913058153"],"related_works":["https://openalex.org/W2136815099","https://openalex.org/W2052483994","https://openalex.org/W2788442932","https://openalex.org/W2063695575","https://openalex.org/W3030900991","https://openalex.org/W2008949385","https://openalex.org/W2156809136","https://openalex.org/W2091184152","https://openalex.org/W1965116372","https://openalex.org/W1751676887"],"abstract_inverted_index":{"Summary":[0],"T":[1,50,87,114,138],"cell":[2,51],"receptor":[3],"mediated":[4],"immunotherapy":[5,39,82],"using":[6,84],"engineered":[7,113],"Hematopoietic":[8,100],"Stem/Progenitor":[9,101],"Cells":[10,102],"leads":[11],"to":[12,43,54,71,191],"durable":[13],"partial":[14],"suppression":[15,23,127],"of":[16,58,141,147],"HIV":[17,59,93,193,198],"in":[18,136,167,200],"humanized":[19,201],"mice.":[20,202],"Sustained":[21],"viral":[22,27,126,142,154,175],"is":[24],"accompanied":[25,131],"by":[26,61,132,181],"evolution":[28,155,199],"under":[29,156],"selection":[30,157],"pressure.":[31],"This":[32],"study":[33],"highlights":[34],"the":[35,41,55,69,106,145,160,168,182],"potential":[36],"for":[37,105,153],"TCR":[38],"and":[40],"need":[42],"target":[44],"multiple":[45],"epitopes.":[46],"Abstract":[47],"Effective":[48],"CD8+":[49],"responses":[52],"targeted":[53],"KK10":[56,169],"epitope":[57,170],"presented":[60],"HLA-B*27:05,":[62],"a":[63,133],"protective":[64],"HLA":[65],"allele,":[66],"correlate":[67],"with":[68,98,118],"ability":[70],"control":[72],"infection":[73,117,194],"without":[74],"antiretroviral":[75],"therapy":[76],"(ART).":[77],"Here,":[78],"we":[79],"report":[80],"an":[81],"approach":[83],"two":[85],"B*27:05-KK10-specific":[86],"Cell":[88],"Receptors":[89],"(TCRs)":[90],"isolated":[91],"from":[92,144,159],"controllers.":[94],"Immunocompromised":[95],"mice":[96,149],"engrafted":[97],"human":[99],"(HSPCs)":[103],"encoding":[104],"TCRs":[107,121],"showed":[108,122,178],"differentiation":[109],"into":[110],"functionally":[111],"active":[112],"cells.":[115,139],"Following":[116],"HIV,":[119],"both":[120],"sustained,":[123],"albeit":[124],"modest,":[125],"over":[128],"32":[129],"weeks,":[130],"concomitant":[134],"increase":[135],"CD4+":[137],"Sequencing":[140],"quasi-species":[143],"plasma":[146],"infected":[148],"demonstrated":[150],"clear":[151],"evidence":[152],"pressure":[158],"TCRs.":[161,183],"The":[162],"most":[163],"commonly":[164],"observed":[165],"mutation":[166],"was":[171,189],"L6M,":[172],"which":[173],"preserved":[174],"fitness":[176],"but":[177],"attenuated":[179],"recognition":[180],"These":[184],"studies":[185],"show":[186],"that":[187],"TCR-immunotherapy":[188],"able":[190],"suppress":[192],"long-term":[195],"while":[196],"driving":[197]},"counts_by_year":[],"updated_date":"2026-09-27T08:07:27.782135","created_date":"2025-10-10T00:00:00"}