{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T12:18:26Z","timestamp":1782476306689,"version":"3.54.5"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2007,6,1]],"date-time":"2007-06-01T00:00:00Z","timestamp":1180656000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>During stationary growth or in vitro conditions mimicking relevant aspects of latency, the HspX protein (Rv2031c) is specifically upregulated by<jats:italic>Mycobacterium tuberculosis<\/jats:italic>. In this study we compared T-cell responses against HspX and the secreted<jats:italic>M. tuberculosis<\/jats:italic>protein Ag85B (Rv1886c) in tuberculosis (TB) patients, tuberculin skin test-positive individuals,<jats:italic>M. bovis<\/jats:italic>BCG-vaccinated individuals, and healthy negative controls. Gamma interferon responses to HspX were significantly higher in<jats:italic>M. tuberculosis<\/jats:italic>-exposed individuals than in<jats:italic>M. tuberculosis<\/jats:italic>-unexposed BCG vaccinees. In contrast, no such differences were found with respect to T-cell responses against Ag85B. Therefore, BCG-based vaccines containing relevant fragments of HspX may induce improved responses against this TB latency antigen. To identify relevant major histocompatibility complex class I- and class II-restricted HspX-specific T-cell epitopes, we immunized HLA-A2\/K<jats:sup>b<\/jats:sup>and HLA-DR3.Ab<jats:sup>0<\/jats:sup>transgenic (tg) mice with HspX. Two new T-cell epitopes were identified, p91-105 and p31-50, restricted via HLA-A*0201 and HLA-DRB1*0301, respectively. These epitopes were recognized by human T cells as well, underlining the relevance of HspX T-cell recognition both in vivo and in vitro. In line with the data in humans, BCG immunization of both tg strains did not lead to T-cell responses against HspX-derived epitopes, whereas nonlatency antigens were efficiently recognized. These data support the notion that BCG vaccination per se does not induce T-cell responses against the latency antigen, HspX. Thus, we suggest that subunit vaccines incorporating HspX and\/or other latency antigens, as well as recombinant BCG strains expressing latency antigens need to be considered as new vaccines against TB.<\/jats:p>","DOI":"10.1128\/iai.01990-06","type":"journal-article","created":{"date-parts":[[2007,3,27]],"date-time":"2007-03-27T01:13:09Z","timestamp":1174957989000},"page":"2914-2921","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":107,"title":["T-Cell Recognition of the HspX Protein of<i>Mycobacterium tuberculosis<\/i>Correlates with Latent<i>M. tuberculosis<\/i>Infection but Not with<i>M. bovis<\/i>BCG Vaccination"],"prefix":"10.1128","volume":"75","author":[{"given":"Annemieke","family":"Geluk","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May Young","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista E.","family":"van Meijgaarden","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliane M. S.","family":"Leyten","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kees L. M. C.","family":"Franken","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom H. M.","family":"Ottenhoff","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miche\u0300l R.","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"392","volume":"114","year":"1998","unstructured":"Agrewala, J. N., and R. J. Wilkinson. 1998. Differential regulation of Th1 and Th2 cells by p91-110 and p21-40 peptides of the 16-kD alpha-crystallin antigen of Mycobacterium tuberculosis. Clin. Exp. Immunol.114:392-397.","journal-title":"Clin. Exp. 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Salerno. 2005. Th0 to Th1 switch of CD4 T-cell clones specific from the 16-kDa antigen of Mycobacterium tuberculosis after successful therapy: lack of involvement of epitope repertoire and HLA-DR. Immunol. Lett.98:253-258.","journal-title":"Lett."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1086\/344174"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200112)31:12<3602::AID-IMMU3602>3.0.CO;2-L"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.4.801-808.1998"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.10.6846-6851.2005"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.13.2.179-186.2006"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.2000.00744.x"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.18.4.687-702.2005"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/prep.1999.1162"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.18.10797"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0161-5890(95)00058-M"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.11.6463"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"5742","DOI":"10.4049\/jimmunol.152.12.5742","volume":"152","year":"1994","unstructured":"Geluk, A., K. E. van Meijgaarden, S. Southwood, C. Oseroff, J. W. Drijfhout, R. R. de Vries, T. H. Ottenhoff, and A. Sette. 1994. HLA-DR3 molecules can bind peptides carrying two alternative specific submotifs. J. Immunol.152:5742-5748.","journal-title":"J. Immunol."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2005.03.001"},{"key":"e_1_3_2_24_2","first-page":"587","volume":"66","year":"1998","unstructured":"Gupte, M. D. 1998. Vaccine trials against leprosy. Int. J. Lepr. Other Mycobact. Dis.66:587-589.","journal-title":"Int. J. Lepr. Other Mycobact. 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