{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:25:38Z","timestamp":1790871938367,"version":"4.1.0"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2000,12,1]],"date-time":"2000-12-01T00:00:00Z","timestamp":975628800000},"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":[[2000,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The role of CD8+ CTL in protection against tuberculosis in human disease is unclear. In this study, we stimulated the peripheral blood mononuclear cells of bacillus Calmette-Gue\u0301rin (BCG)-vaccinated individuals with live Mycobacterium bovis BCG bacilli to establish short-term cell lines and then purified the CD8+ T cells. A highly sensitive enzyme-linked immunospot (ELISPOT) assay for single cell IFN-\u03b3 release was used to screen CD8+ T cells with overlapping peptides spanning the mycobacterial major secreted protein, Ag85A. Three peptides consistently induced a high frequency of IFN-\u03b3 responsive CD8+ T cells, and two HLA-A*0201 binding motifs, P48\u201356 and P242\u2013250, were revealed within the core sequences. CD8+ T cells responding to the 9-mer epitopes were visualized within fresh blood by ELISPOT using free peptide or by binding of HLA-A*0201 tetrameric complexes. The class I-restricted CD8+ T cells were potent CTL effector cells that efficiently lysed an HLA-A2-matched monocyte cell line pulsed with peptide as well as autologous macrophages infected with Mycobacterium tuberculosis or recombinant vaccinia virus expressing the whole Ag85A protein. Tetramer assays revealed a 6-fold higher frequency of peptide-specific T cells than IFN-\u03b3 ELISPOT assays, indicating functional heterogeneity within the CD8+ T cell population. These results demonstrate a previously unrecognized, MHC class I-restricted, CD8+ CTL response to a major secreted Ag of mycobacteria and supports the use of Ag85A as a candidate vaccine against tuberculosis.<\/jats:p>","DOI":"10.4049\/jimmunol.165.12.7088","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:33:40Z","timestamp":1398022420000},"page":"7088-7095","source":"Crossref","is-referenced-by-count":83,"title":["Human CD8+ CTL Specific for the Mycobacterial Major Secreted Antigen 85A"],"prefix":"10.1093","volume":"165","author":[{"given":"Steven M","family":"Smith","sequence":"first","affiliation":[{"name":"Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , Keppel Street, London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Brookes","sequence":"additional","affiliation":[{"name":"Molecular Immunology Group, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital , Oxford ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miche\u0300l R","family":"Klein","sequence":"additional","affiliation":[{"name":"Tuberculosis Research Programme, MRC Laboratories , Fajara ,","place":["The Gambia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam S","family":"Malin","sequence":"additional","affiliation":[{"name":"Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , Keppel Street, London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline T","family":"Lukey","sequence":"additional","affiliation":[{"name":"Glaxo-Wellcome Research and Development, Medicines Research Centre , Stevenage ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail S","family":"King","sequence":"additional","affiliation":[{"name":"Molecular Immunology Group, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital , Oxford ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham S","family":"Ogg","sequence":"additional","affiliation":[{"name":"Molecular Immunology Group, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital , Oxford ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian V S","family":"Hill","sequence":"additional","affiliation":[{"name":"Molecular Immunology Group, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital , Oxford ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazel M","family":"Dockrell","sequence":"additional","affiliation":[{"name":"Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , Keppel Street, London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,12,15]]},"reference":[{"key":"2025032908200370700_R1","first-page":"220","volume-title":"J. Am. Med. Assoc.","year":"1995"},{"key":"2025032908200370700_R2","first-page":"1055","volume-title":"Science","year":"1992"},{"key":"2025032908200370700_R3","first-page":"3482","volume-title":"Infect. Immun.","year":"1993"},{"key":"2025032908200370700_R4","first-page":"197","volume-title":"Infect. Immun.","year":"1993"},{"key":"2025032908200370700_R5","first-page":"2737","volume-title":"Infect. Immun.","year":"1991"},{"key":"2025032908200370700_R6","first-page":"518","volume-title":"J. Immunol.","year":"1993"},{"key":"2025032908200370700_R7","first-page":"3359","volume-title":"J. Immunol.","year":"1995"},{"key":"2025032908200370700_R8","first-page":"1949","volume-title":"J. Immunol.","year":"1997"},{"key":"2025032908200370700_R9","first-page":"327","volume-title":"J. Immunol.","year":"1999"},{"key":"2025032908200370700_R10","first-page":"12013","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1992"},{"key":"2025032908200370700_R11","first-page":"377","volume-title":"Eur. J. Immunol.","year":"1995"},{"key":"2025032908200370700_R12","first-page":"290","volume-title":"J. Immunol.","year":"1997"},{"key":"2025032908200370700_R13","first-page":"339","volume-title":"Immunology","year":"1996"},{"key":"2025032908200370700_R14","first-page":"1633","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2025032908200370700_R15","first-page":"5223","volume-title":"Infect. Immun.","year":"1999"},{"key":"2025032908200370700_R16","first-page":"419","volume-title":"Clin. Exp. Immunol.","year":"1996"},{"key":"2025032908200370700_R17","first-page":"129","volume-title":"Annu. Rev. Immunol.","year":"1993"},{"key":"2025032908200370700_R18","first-page":"1317","volume-title":"Infect. Immun.","year":"1997"},{"key":"2025032908200370700_R19","first-page":"127","volume-title":"Infect. Immun.","year":"1997"},{"key":"2025032908200370700_R20","first-page":"830","volume-title":"Infect. Immun.","year":"1998"},{"key":"2025032908200370700_R21","first-page":"3242","volume-title":"Infect. Immun.","year":"1999"},{"key":"2025032908200370700_R22","first-page":"3980","volume-title":"Infect. Immun.","year":"1999"},{"key":"2025032908200370700_R23","first-page":"270","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1998"},{"key":"2025032908200370700_R24","first-page":"2400","volume-title":"J. Immunol.","year":"1998"},{"key":"2025032908200370700_R25","first-page":"585","volume-title":"Immunology","year":"1998"},{"key":"2025032908200370700_R26","first-page":"1527","volume-title":"Infect. Immun.","year":"1998"},{"key":"2025032908200370700_R27","first-page":"888","volume-title":"Nat. Med.","year":"1996"},{"key":"2025032908200370700_R28","first-page":"269","volume-title":"Nature","year":"1999"},{"key":"2025032908200370700_R29","first-page":"648","volume-title":"Microbiol. Rev.","year":"1992"},{"key":"2025032908200370700_R30","first-page":"676","volume-title":"Infect. Immun.","year":"1997"},{"key":"2025032908200370700_R31","first-page":"209","volume-title":"Int. Immunol.","year":"1999"},{"key":"2025032908200370700_R32","first-page":"3679","volume-title":"Infect. Immun.","year":"1994"},{"key":"2025032908200370700_R33","first-page":"363","volume-title":"Infect. Immun.","year":"1994"},{"key":"2025032908200370700_R34","first-page":"726","volume-title":"Infect. Immun.","year":"1994"},{"key":"2025032908200370700_R35","first-page":"893","volume-title":"Nat. Med.","year":"1996"},{"key":"2025032908200370700_R36","first-page":"251","volume-title":"Tuberc. Lung Dis.","year":"1999"},{"key":"2025032908200370700_R37","first-page":"859","volume-title":"J. Exp. Med.","year":"1997"},{"key":"2025032908200370700_R38","first-page":"2103","volume-title":"Science","year":"1998"},{"key":"2025032908200370700_R39","first-page":"4342","volume-title":"J. Immunol.","year":"1999"},{"key":"2025032908200370700_R40","first-page":"1016","volume-title":"Lancet","year":"1990"},{"key":"2025032908200370700_R41","first-page":"1203","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2025032908200370700_R42","first-page":"6959","volume-title":"J. Immunol.","year":"1999"},{"key":"2025032908200370700_R43","first-page":"413","volume-title":"Curr. Biol.","year":"1998"},{"key":"2025032908200370700_R44","first-page":"1827","volume-title":"J. Immunol.","year":"1999"},{"key":"2025032908200370700_R45","first-page":"1641","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2025032908200370700_R46","first-page":"1780","volume-title":"J. Immunol.","year":"1999"},{"key":"2025032908200370700_R47","first-page":"1765","volume-title":"J. Immunol.","year":"1999"},{"key":"2025032908200370700_R48","first-page":"2227","volume-title":"J. Immunol.","year":"1999"},{"key":"2025032908200370700_R49","first-page":"5692","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1999"},{"key":"2025032908200370700_R50","first-page":"677","volume-title":"Nat. Med.","year":"1999"},{"key":"2025032908200370700_R51","first-page":"63","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2025032908200370700_R52","first-page":"6721","volume-title":"J. Virol.","year":"1999"},{"key":"2025032908200370700_R53","first-page":"9153","volume-title":"J. Virol.","year":"1999"},{"key":"2025032908200370700_R54","first-page":"11786","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1996"},{"key":"2025032908200370700_R55","first-page":"13146","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1997"},{"key":"2025032908200370700_R56","first-page":"257","volume-title":"J. Exp. Med.","year":"1995"},{"key":"2025032908200370700_R57","first-page":"305","volume-title":"Infect. Immun.","year":"1997"},{"key":"2025032908200370700_R58","first-page":"15190","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1999"},{"key":"2025032908200370700_R59","first-page":"1205","volume-title":"Microbiology","year":"1998"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/165\/12\/7088\/62728879\/7088.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/165\/12\/7088\/62728879\/7088.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T05:58:01Z","timestamp":1743400681000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/165\/12\/7088\/8038822"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,12]]},"references-count":59,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2000,12,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.165.12.7088","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2000,12]]},"published":{"date-parts":[[2000,12]]}}}