{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:00:35Z","timestamp":1791356435144,"version":"4.3.1"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,4,5]]},"abstract":"<jats:p>\n                    The 6-kDa early secretory antigenic target of\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (ESAT-6) and the 10-kDa culture filtrate antigen (CFP-10), encoded in region of difference 1 (RD1) and secreted by the ESAT-6 system 1 (Esx-1) secretion system, are the most immunodominant and highly\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    (MTB)-specific antigens. These attributes are responsible for their primary importance in tuberculosis (TB) immunodiagnosis and vaccine development. Rv3615c [Esx-1 substrate protein C (EspC)], encoded outside RD1, is similar in size and sequence homology to CFP-10 and ESAT-6, suggesting it might be a target of cellular immunity in TB. Using ex vivo enzyme-linked immunospot- and flow cytometry-based cytokine-secretion assay, we comprehensively assessed cellular immune responses to EspC in patients with active TB, latently infected persons, and uninfected bacillus Calmette\u2013Gu\u00e9rin (BCG)-vaccinated controls. EspC was at least as immunodominant as ESAT-6 and CFP-10 in both active and latent TB infection. EspC contained broadly recognized CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    epitopes, inducing a predominantly CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell response that comprised functional T-cell subsets secreting both IFN-\u03b3 and IL-2 as well as functional T-cell subsets secreting only IFN-\u03b3. Surprisingly, T-cell responses to EspC were as highly specific (93%) for MTB infection as responses to ESAT-6 and CFP-10, with only 2 of 27 BCG-vaccinated controls responding to each antigen. Using quantitative proteomics and metabolically labeled mutant and genetically complemented MTB strains, we identified the mechanism of the specificity of anti-EspC immunity as the Esx-1 dependence of EspC secretion. The high immunodominance of EspC, equivalent to that of ESAT-6 and CFP-10, makes it a TB vaccine candidate, and its high specificity confers strong potential for T-cell\u2013based immunodiagnosis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1015153108","type":"journal-article","created":{"date-parts":[[2011,3,22]],"date-time":"2011-03-22T22:40:46Z","timestamp":1300833646000},"page":"5730-5735","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":129,"title":["Rv3615c is a highly immunodominant RD1 (Region of Difference 1)-dependent secreted antigen specific for\n                    <i>Mycobacterium tuberculosis<\/i>\n                    infection"],"prefix":"10.1073","volume":"108","author":[{"given":"Kerry A.","family":"Millington","sequence":"first","affiliation":[{"name":"Tuberculosis Research Unit, National Heart and Lung Institute, Imperial College London, London, W2 1PG, United Kingdom;"},{"name":"Tuberculosis Service, St Mary's Hospital, Imperial College Healthcare, National Health Service Trust, London, W2 1PG, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"Fortune","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health, Harvard University, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Low","sequence":"additional","affiliation":[{"name":"Tuberculosis Research Unit, National Heart and Lung Institute, Imperial College London, London, W2 1PG, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Garces","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health, Harvard University, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne 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