{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:58:06Z","timestamp":1787061486699,"version":"build-2736575974"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T00:00:00Z","timestamp":1657152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1ZIAAI001029"],"award-info":[{"award-number":["1ZIAAI001029"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Antigen-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells play a key role in the host\u2019s antiviral response. T cells recognize viral epitopes via the T cell receptor (TCR), which contains the complementarity-determining region-3 (CDR3), comprising the variable, diversity and joining regions of the TCR\u03b2 gene. During chronic simian immunodeficiency virus (SIV) infection of Asian macaque nonhuman primates, tissue-specific clonotypes are identifiable among SIV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Here, we sought to determine level of antigen exposure responsible for the tissue-specific clonotypic structure. We examined whether the priming event and\/or chronic antigen exposure is response for tissue-specific TCR repertoires. We evaluated the TCR repertoire of SIV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells after acute antigen exposure following inoculation with a SIV DNA vaccine, longitudinally during the acute and chronic phases of SIV, and after administration of antiretrovirals (ARVs). Finally, we assessed the TCR repertoire of cytomegalovirus (CMV)-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells to establish if TCR tissue-specificity is shared among viruses that chronically replicate. TCR sequences unique to anatomical sites were identified after acute antigen exposure via vaccination and upon acute SIV infection. Tissue-specific clones also persisted into chronic infection and the clonotypic structure continued to evolve after ARV administration. Finally, tissue-specific clones were also observed in CMV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Together, these data suggest that acute antigen priming is sufficient to induce tissue-specific clones and that this clonal hierarchy can persist when antigen loads are naturally or therapeutically reduced, providing mechanistic insight into tissue-residency.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010611","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T13:25:29Z","timestamp":1657200329000},"page":"e1010611","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Multiple modes of antigen exposure induce clonotypically diverse epitope-specific CD8+ T cells across multiple tissues in nonhuman primates"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8462-1688","authenticated-orcid":true,"given":"Jennifer","family":"Simpson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carly E.","family":"Starke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra M.","family":"Ortiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Ransier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Darko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Douek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8357-2984","authenticated-orcid":true,"given":"Jason M.","family":"Brenchley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,7,7]]},"reference":[{"issue":"10","key":"ppat.1010611.ref001","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1084\/jem.20070784","article-title":"Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover","volume":"204","author":"JR Almeida","year":"2007","journal-title":"J Exp Med"},{"issue":"3","key":"ppat.1010611.ref002","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1097\/COH.0b013e3283454c39","article-title":"Qualitative features of the HIV-specific CD8+ T-cell response associated with immunologic control","volume":"6","author":"AR Hersperger","year":"2011","journal-title":"Curr Opin HIV AIDS"},{"issue":"1","key":"ppat.1010611.ref003","doi-asserted-by":"crossref","first-page":"e1000747","DOI":"10.1371\/journal.ppat.1000747","article-title":"CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells","volume":"6","author":"NR Klatt","year":"2010","journal-title":"PLoS Pathog"},{"issue":"8","key":"ppat.1010611.ref004","doi-asserted-by":"crossref","first-page":"4005","DOI":"10.1128\/JVI.02785-15","article-title":"Expansion of Inefficient HIV-Specific CD8 T Cells during Acute Infection","volume":"90","author":"MA Eller","year":"2016","journal-title":"J Virol"},{"issue":"21","key":"ppat.1010611.ref005","doi-asserted-by":"crossref","first-page":"10515","DOI":"10.1128\/JVI.75.21.10515-10519.2001","article-title":"Emergence and kinetics of simian immunodeficiency virus-specific CD8(+) T cells in the intestines of macaques during primary infection","volume":"75","author":"RS Veazey","year":"2001","journal-title":"J Virol"},{"issue":"2","key":"ppat.1010611.ref006","doi-asserted-by":"crossref","first-page":"e1003195","DOI":"10.1371\/journal.ppat.1003195","article-title":"Cytotoxic capacity of SIV-specific CD8(+) T cells against primary autologous targets correlates with immune control in SIV-infected rhesus macaques","volume":"9","author":"D Mendoza","year":"2013","journal-title":"PLoS Pathog"},{"issue":"12","key":"ppat.1010611.ref007","doi-asserted-by":"crossref","first-page":"e1006135","DOI":"10.1371\/journal.ppat.1006135","article-title":"Collapse of Cytolytic Potential in SIV-Specific CD8+ T Cells Following Acute SIV Infection in Rhesus Macaques","volume":"12","author":"ER Roberts","year":"2016","journal-title":"PLoS Pathog"},{"issue":"6","key":"ppat.1010611.ref008","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.immuni.2004.10.010","article-title":"T cell receptor recognition motifs govern immune escape patterns in acute SIV infection","volume":"21","author":"DA Price","year":"2004","journal-title":"Immunity"},{"key":"ppat.1010611.ref009","article-title":"SIV-specific CD8+ T cells are clonotypically distinct across lymphoid and mucosal tissues","author":"CE Starke","year":"2019","journal-title":"J Clin Invest"},{"issue":"202\u2013213","key":"ppat.1010611.ref010","article-title":"Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection","volume":"20","author":"MJ Cannon","year":"2010","journal-title":"Rev Med Virol"},{"issue":"6","key":"ppat.1010611.ref011","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1586\/14789450.2014.971116","article-title":"The life cycle and pathogenesis of human cytomegalovirus infection: lessons from proteomics","volume":"11","author":"PM Jean Beltran","year":"2014","journal-title":"Expert Rev 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Nephrol"},{"issue":"6","key":"ppat.1010611.ref015","doi-asserted-by":"crossref","first-page":"4188","DOI":"10.4049\/jimmunol.181.6.4188","article-title":"Trafficking of antigen-specific CD8+ T lymphocytes to mucosal surfaces following intramuscular vaccination","volume":"181","author":"DR Kaufman","year":"2008","journal-title":"J Immunol"},{"issue":"16","key":"ppat.1010611.ref016","doi-asserted-by":"crossref","first-page":"7485","DOI":"10.1128\/JVI.74.16.7485-7495.2000","article-title":"Simian immunodeficiency virus (SIV) gag DNA-vaccinated rhesus monkeys develop secondary cytotoxic T-lymphocyte responses and control viral replication after pathogenic SIV infection","volume":"74","author":"MA Egan","year":"2000","journal-title":"Journal of virology"},{"issue":"2","key":"ppat.1010611.ref017","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.virol.2006.06.036","article-title":"A DNA prime-oral Listeria boost vaccine in rhesus macaques induces a SIV-specific CD8 T cell 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Immune Surveillance in Nonlymphoid Organs","volume":"195","author":"FR Carbone","year":"2015","journal-title":"J Immunol"},{"issue":"6","key":"ppat.1010611.ref026","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1084\/jem.20151855","article-title":"Local antigen in nonlymphoid tissue promotes resident memory CD8+ T cell formation during viral infection","volume":"213","author":"TN Khan","year":"2016","journal-title":"Journal of Experimental Medicine"},{"issue":"13","key":"ppat.1010611.ref027","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1084\/jem.20160888","article-title":"Antigen-dependent competition shapes the local repertoire of tissue-resident memory CD8+ T cells","volume":"213","author":"A Muschaweckh","year":"2016","journal-title":"Journal of Experimental Medicine"},{"issue":"1","key":"ppat.1010611.ref028","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.immuni.2020.10.022","article-title":"Competition for Active TGF\u03b2 Cytokine Allows for Selective Retention of Antigen-Specific Tissue- Resident Memory T Cells in the Epidermal Niche","volume":"54","author":"T Hirai","year":"2021","journal-title":"Immunity"},{"issue":"9","key":"ppat.1010611.ref029","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1038\/s41590-021-01004-1","article-title":"Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity","volume":"22","author":"SN Christo","year":"2021","journal-title":"Nature Immunology"},{"issue":"24","key":"ppat.1010611.ref030","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.aar4526","article-title":"Identification and characterization of HIV-specific resident memory CD8(+) T cells in human lymphoid tissue","volume":"3","author":"M Buggert","year":"2018","journal-title":"Sci Immunol"},{"issue":"1","key":"ppat.1010611.ref031","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.virol.2004.01.022","article-title":"Number of CD4+ and CD8+ T-cell CDR3 clonotypes expanding during acute infection of macaques with simian immunodeficiency virus","volume":"322","author":"F Bernardin","year":"2004","journal-title":"Virology"},{"issue":"3","key":"ppat.1010611.ref032","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nri2260","article-title":"The molecular basis for public T-cell responses?","volume":"8","author":"V Venturi","year":"2008","journal-title":"Nature Reviews Immunology"},{"issue":"4","key":"ppat.1010611.ref033","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.4049\/jimmunol.1001340","article-title":"Clonal repertoires of virus-specific CD8+ T lymphocytes are shared in mucosal and systemic compartments during chronic simian immunodeficiency virus infection in rhesus monkeys","volume":"185","author":"P Sircar","year":"2010","journal-title":"J Immunol"},{"key":"ppat.1010611.ref034","first-page":"644","article-title":"Dynamic Perturbations of the T-Cell Receptor Repertoire in Chronic HIV Infection and following Antiretroviral Therapy","volume":"6","author":"JM Heather","year":"2015","journal-title":"Front Immunol"},{"issue":"7","key":"ppat.1010611.ref035","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1093\/intimm\/13.7.941","article-title":"The flexibility of the TCR allows recognition of a large set of naturally occurring epitope variants by HIV-specific cytotoxic T lymphocytes","volume":"13","author":"F Buseyne","year":"2001","journal-title":"International immunology"},{"issue":"3","key":"ppat.1010611.ref036","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.4049\/jimmunol.1102610","article-title":"Clonotype and repertoire changes drive the functional improvement of HIV-specific CD8 T cell populations under conditions of limited antigenic stimulation","volume":"188","author":"L Janbazian","year":"2012","journal-title":"J Immunol"},{"issue":"4","key":"ppat.1010611.ref037","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.cell.2015.03.031","article-title":"Quantifying Memory CD8 T Cells Reveals Regionalization of Immunosurveillance","volume":"161","author":"M Steinert Elizabeth","year":"2015","journal-title":"Cell"},{"issue":"2","key":"ppat.1010611.ref038","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.immuni.2017.01.009","article-title":"CD49a Expression Defines Tissue-Resident CD8(+) T Cells Poised for Cytotoxic Function in Human Skin","volume":"46","author":"S Cheuk","year":"2017","journal-title":"Immunity"},{"issue":"1","key":"ppat.1010611.ref039","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s41587-021-00989-2","article-title":"Integrating T cell receptor sequences and transcriptional profiles by clonotype neighbor graph analysis (CoNGA)","volume":"40","author":"SA Schattgen","year":"2022","journal-title":"Nature Biotechnology"},{"issue":"9","key":"ppat.1010611.ref040","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1038\/s41591-018-0132-5","article-title":"Experimental microbial dysbiosis does not promote disease progression in SIV-infected macaques","volume":"24","author":"AM Ortiz","year":"2018","journal-title":"Nat Med"},{"issue":"2","key":"ppat.1010611.ref041","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1089\/aid.2015.0130","article-title":"Short Communication: Comparative Evaluation of Coformulated Injectable Combination Antiretroviral Therapy Regimens in Simian Immunodeficiency Virus-Infected Rhesus Macaques","volume":"32","author":"GQ Del Prete","year":"2016","journal-title":"AIDS research and human retroviruses"},{"issue":"5","key":"ppat.1010611.ref042","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.4049\/jimmunol.1900377","article-title":"Primary EBV Infection Induces an Acute Wave of Activated Antigen-Specific Cytotoxic CD4(+) T Cells","volume":"203","author":"BJ Meckiff","year":"2019","journal-title":"J Immunol"},{"issue":"5","key":"ppat.1010611.ref043","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.4049\/jimmunol.1701377","article-title":"CCR8 Expression Defines Tissue-Resident Memory T Cells in Human Skin","volume":"200","author":"ML McCully","year":"2018","journal-title":"J Immunol"},{"issue":"4","key":"ppat.1010611.ref044","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1084\/jem.20081127","article-title":"Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection","volume":"206","author":"DA Price","year":"2009","journal-title":"J Exp Med"},{"key":"ppat.1010611.ref045","first-page":"Unit10 33","article-title":"Unbiased molecular analysis of T cell receptor expression using template-switch anchored RT-PCR","volume":"Chapter 10","author":"MF Quigley","year":"2011","journal-title":"Curr Protoc Immunol"},{"issue":"2","key":"ppat.1010611.ref046","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/bjh.16053","article-title":"T-cell receptor sequencing demonstrates persistence of virus-specific T cells after antiviral immunotherapy","volume":"187","author":"MD Keller","year":"2019","journal-title":"Br J Haematol"},{"issue":"7","key":"ppat.1010611.ref047","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s00251-009-0383-x","article-title":"A clonotype nomenclature for T cell receptors","volume":"61","author":"MB Yassai","year":"2009","journal-title":"Immunogenetics"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010611","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T22:09:35Z","timestamp":1676066975000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010611"}},"subtitle":[],"editor":[{"given":"Benjamin N.","family":"Bimber","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,7,7]]},"references-count":47,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1010611","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,7]]}}}