{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:12:18Z","timestamp":1790111538056,"version":"4.0.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"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":[[2015,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Human T cells are activated by both peptide and nonpeptide Ags produced by Mycobacterium tuberculosis. T cells recognize cell wall lipids bound to CD1 molecules, but effector functions of CD1-reactive T cells have not been systematically assessed in M. tuberculosis\u2013infected humans. It is also not known how these features correlate with T cell responses to secreted protein Ags. We developed a flow cytometric assay to profile CD1-restricted T cells ex vivo and assessed T cell responses to five cell wall lipid Ags in a cross-sectional study of 19 M. tuberculosis\u2013infected and 22 M. tuberculosis\u2013uninfected South African adolescents. We analyzed six T cell functions using a recently developed computational approach for flow cytometry data in high dimensions. We compared these data with T cell responses to five protein Ags in the same cohort. We show that CD1b-restricted T cells producing antimycobacterial cytokines IFN-\u03b3 and TNF-\u03b1 are detectable ex vivo in CD4+, CD8+, and CD4\u2212CD8\u2212 T cell subsets. Glucose monomycolate was immunodominant among lipid Ags tested, and polyfunctional CD4 T cells specific for this lipid simultaneously expressed CD40L, IFN-\u03b3, IL-2, and TNF-\u03b1. Lipid-reactive CD4+ T cells were detectable at frequencies of 0.001\u20130.01%, and this did not differ by M. tuberculosis infection status. Finally, CD4 T cell responses to lipids were poorly correlated with CD4 T cell responses to proteins (Spearman rank correlation \u22120.01; p = 0.95). These results highlight the functional diversity of CD1-restricted T cells circulating in peripheral blood as well as the complementary nature of T cell responses to mycobacterial lipids and proteins. Our approach enables further population-based studies of lipid-specific T cell responses during natural infection and vaccination.<\/jats:p>","DOI":"10.4049\/jimmunol.1501285","type":"journal-article","created":{"date-parts":[[2015,10,15]],"date-time":"2015-10-15T03:28:31Z","timestamp":1444879711000},"page":"4595-4603","source":"Crossref","is-referenced-by-count":20,"title":["T Cell Responses against Mycobacterial Lipids and Proteins Are Poorly Correlated in South African Adolescents"],"prefix":"10.1093","volume":"195","author":[{"given":"Chetan","family":"Seshadri","sequence":"first","affiliation":[{"name":"Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lin","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J","family":"Scriba","sequence":"additional","affiliation":[{"name":"South African TB Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town , Cape Town 7700 ,","place":["South Africa"]},{"name":"Department of Pediatrics and Child Health, Institute of Infectious Disease and Molecular Medicine, University of Cape Town , Cape Town 7700 ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenna","family":"Peterson","sequence":"additional","affiliation":[{"name":"Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Freidrich","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"},{"name":"HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Frahm","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"},{"name":"HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C","family":"DeRosa","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"},{"name":"HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"},{"name":"Department of Laboratory Medicine, University of Washington , Seattle WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D Branch","family":"Moody","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Brigham and Women\u2019s Hospital , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Prandi","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, Centre National de la Recherche Scientifique , Toulouse 31077 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Gilleron","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, Centre National de la Recherche Scientifique , Toulouse 31077 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Mahomed","sequence":"additional","affiliation":[{"name":"Division of Community Health, Stellenbosch University , Stellanbosch 7602 ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Finak","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem A","family":"Hanekom","sequence":"additional","affiliation":[{"name":"South African TB Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town , Cape Town 7700 ,","place":["South Africa"]},{"name":"Department of Pediatrics and Child Health, Institute of Infectious Disease and Molecular Medicine, University of Cape Town , Cape Town 7700 ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Gottardo","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Juliana","family":"McElrath","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"},{"name":"HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R","family":"Hawn","sequence":"additional","affiliation":[{"name":"Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington , Seattle, WA 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