{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T03:24:03Z","timestamp":1789097043254,"version":"build-2803163510"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2001,8,1]],"date-time":"2001-08-01T00:00:00Z","timestamp":996624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>High steady-state frequencies of CMV-specific CD4+ memory T cells are maintained in CMV-exposed subjects, and these cells are thought to play a key role in the immunologic control of this permanent infection. However, the essential components of this response are poorly defined. Here, we report the use of a step-wise application of flow cytometric and molecular techniques to determine the number and size of the TCR V\u03b2-defined clonotypes within freshly obtained CMV-specific CD4+ memory T cell populations of four healthy, CMV-exposed human subjects. This analysis revealed a stable clonotypic hierarchy in which 1\u20133 dominant clonotypes are maintained in concert with more numerous subdominant and minor clonotypes. These dominant clonotypes accounted for 10\u201350% of the overall CMV response, and comprised from 0.3 to 4.0% of peripheral blood CD4+ T cells. Two subjects displayed immunodominant responses to single epitopes within the CMV matrix phosphoprotein pp65; these single epitope responses were mediated by a single dominant clonotype in one subject, and by multiple subdominant and minor clonotypes in the other. Thus, the CMV-specific CD4+ T cell memory repertoire in normal subjects is characterized by striking clonotypic dominance and the potential for epitope focusing, suggesting that primary responsibility for immunosurveillance against CMV reactivation rests with a handful of clones recognizing a limited array of CMV determinants. These data have important implications for the understanding of mechanisms by which a genetically stable chronic viral pathogen such as CMV is controlled, and offer possible insight into the failure of such control for a genetically flexible pathogen like HIV-1.<\/jats:p>","DOI":"10.4049\/jimmunol.167.3.1151","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T23:31:49Z","timestamp":1398123109000},"page":"1151-1163","source":"Crossref","is-referenced-by-count":71,"title":["Clonotypic Structure of the Human CD4+ Memory T Cell Response to Cytomegalovirus"],"prefix":"10.1093","volume":"167","author":[{"given":"Arlene D","family":"Bitmansour","sequence":"first","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health Sciences University , Portland, OR 97201"},{"name":"Graduate Program in Immunology, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shar L","family":"Waldrop","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health Sciences University , Portland, OR 97201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine J","family":"Pitcher","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health Sciences University , Portland, OR 97201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Khatamzas","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health Sciences University , Portland, OR 97201"},{"name":"Institut fu\u0308r Medizinische Immunologie , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Kern","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Medizinische Immunologie , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vernon C","family":"Maino","sequence":"additional","affiliation":[{"name":"Becton Dickinson Biosciences , San Jose, CA 95131"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis J","family":"Picker","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health Sciences University , Portland, OR 97201"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2001,8,1]]},"reference":[{"key":"2026020209133298200_R1","first-page":"725","volume-title":"Persistent Viral Infections","year":"1999"},{"key":"2026020209133298200_R2","first-page":"8056","volume-title":"J. Virol.","year":"1994"},{"key":"2026020209133298200_R3","first-page":"2205","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2026020209133298200_R4","first-page":"5135","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1999"},{"key":"2026020209133298200_R5","first-page":"189","volume-title":"Nat. Med.","year":"1999"},{"key":"2026020209133298200_R6","first-page":"1713","volume-title":"J. Exp. Med.","year":"1994"},{"key":"2026020209133298200_R7","first-page":"209","volume-title":"Persistent Viral Infections","year":"1999"},{"key":"2026020209133298200_R8","first-page":"702","volume-title":"J. Infect. Dis.","year":"1999"},{"key":"2026020209133298200_R9","first-page":"181","volume-title":"Rev. Med. Virol.","year":"1997"},{"key":"2026020209133298200_R10","first-page":"1069","volume-title":"J. Acquired Immune Defic. Syndr.","year":"1992"},{"key":"2026020209133298200_R11","first-page":"324","volume-title":"J. Acquired Immune Defic. Syndr. Hum. Retrovirol.","year":"1995"},{"key":"2026020209133298200_R12","first-page":"953","volume-title":"Nat. Med.","year":"1998"},{"key":"2026020209133298200_R13","first-page":"546","volume-title":"Science","year":"1999"},{"key":"2026020209133298200_R14","first-page":"5284","volume-title":"J. Immunol.","year":"1998"},{"key":"2026020209133298200_R15","first-page":"1739","volume-title":"J. Clin. Invest.","year":"1997"},{"key":"2026020209133298200_R16","first-page":"518","volume-title":"Nat. Med.","year":"1999"},{"key":"2026020209133298200_R17","first-page":"4382","volume-title":"Eur. J. Immunol.","year":"1998"},{"key":"2026020209133298200_R18","first-page":"4924","volume-title":"J. Immunol.","year":"2000"},{"key":"2026020209133298200_R19","first-page":"1261","volume-title":"J. Exp. Med.","year":"1994"},{"key":"2026020209133298200_R20","first-page":"262","volume-title":"Immunol. Today","year":"1999"},{"key":"2026020209133298200_R21","first-page":"2842","volume-title":"J. Immunol.","year":"1998"},{"key":"2026020209133298200_R22","first-page":"2099","volume-title":"J. Virol.","year":"1999"},{"key":"2026020209133298200_R23","first-page":"7569","volume-title":"J. Virol.","year":"1996"},{"key":"2026020209133298200_R24","first-page":"8179","volume-title":"J. Virol.","year":"1999"},{"key":"2026020209133298200_R25","first-page":"446","volume-title":"Methods Enzymol.","year":"1993"},{"key":"2026020209133298200_R26","first-page":"1023","volume-title":"Am. J. Pathol.","year":"1999"},{"key":"2026020209133298200_R27","first-page":"2972","volume-title":"Eur. J. Immunol.","year":"1993"},{"key":"2026020209133298200_R28","first-page":"104","volume-title":"Science","year":"1996"},{"key":"2026020209133298200_R29","first-page":"757","volume-title":"J. Exp. Med.","year":"1997"},{"key":"2026020209133298200_R30","first-page":"5109","volume-title":"J. Immunol.","year":"1994"},{"key":"2026020209133298200_R31","first-page":"176","volume-title":"Immunol. Today","year":"1995"},{"key":"2026020209133298200_R32","first-page":"1021","volume-title":"BioTechniques","year":"1994"},{"key":"2026020209133298200_R33","first-page":"1777","volume-title":"J. Immunol.","year":"1993"},{"key":"2026020209133298200_R34","first-page":"3763","volume-title":"J. Biol. Chem.","year":"1996"},{"key":"2026020209133298200_R35","first-page":"68","volume-title":"J. Med. Virol.","year":"1997"},{"key":"2026020209133298200_R36","first-page":"153","volume-title":"J. Gen. Virol.","year":"1995"},{"key":"2026020209133298200_R37","first-page":"479","volume-title":"Fundamental Immunology","year":"1998"},{"key":"2026020209133298200_R38","first-page":"51","volume-title":"Annu. Rev. Immunol.","year":"1999"},{"key":"2026020209133298200_R39","first-page":"60","volume-title":"Science","year":"1996"},{"key":"2026020209133298200_R40","first-page":"83","volume-title":"Annu. Rev. Immunol.","year":"2000"},{"key":"2026020209133298200_R41","first-page":"4831","volume-title":"J. Immunol.","year":"2000"},{"key":"2026020209133298200_R42","first-page":"906","volume-title":"Nat. Med.","year":"1996"},{"key":"2026020209133298200_R43","first-page":"5729","volume-title":"J. Immunol.","year":"2000"},{"key":"2026020209133298200_R44","first-page":"463","volume-title":"Nature","year":"1994"},{"key":"2026020209133298200_R45","first-page":"785","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2026020209133298200_R46","first-page":"4525","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020209133298200_R47","first-page":"561","volume-title":"Annu. Rev. Immunol.","year":"2000"},{"key":"2026020209133298200_R48","first-page":"119","volume-title":"Cell","year":"1997"},{"key":"2026020209133298200_R49","first-page":"157","volume-title":"Transpl. Infect. Dis.","year":"1999"},{"key":"2026020209133298200_R50","first-page":"1823","volume-title":"J. Exp. Med.","year":"1999"},{"key":"2026020209133298200_R51","first-page":"386","volume-title":"Nature","year":"2000"},{"key":"2026020209133298200_R52","first-page":"177","volume-title":"Cell","year":"1995"},{"key":"2026020209133298200_R53","first-page":"1319","volume-title":"J. Exp. Med.","year":"1999"},{"key":"2026020209133298200_R54","first-page":"733","volume-title":"Immunity","year":"1999"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/167\/3\/1151\/62546532\/1151.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/167\/3\/1151\/62546532\/1151.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T14:18:20Z","timestamp":1770041900000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/167\/3\/1151\/8025712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,8,1]]},"references-count":54,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2001,8,1]]},"published-print":{"date-parts":[[2001,8,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.167.3.1151","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2001,8]]},"published":{"date-parts":[[2001,8,1]]}}}