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Mycobacterium-expanded \u03b3<jats:sub>9<\/jats:sub>\u03b4<jats:sub>2<\/jats:sub>T cells represent only a subset of the phosphoantigen {isopentenyl pyrophosphate [IPP] and (<jats:italic>E<\/jats:italic>)-4-hydroxy-3-methyl-but-2-enylpyrophosphate [HMBPP]}-responsive \u03b3<jats:sub>9<\/jats:sub>\u03b4<jats:sub>2<\/jats:sub>T cells, expressing an oligoclonal set of T cell receptor (TCR) sequences which more efficiently recognize and inhibit intracellular<jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>infection. Based on this premise, we have been searching for<jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>antigens specifically capable of inducing a unique subset of mycobacterium-protective \u03b3<jats:sub>9<\/jats:sub>\u03b4<jats:sub>2<\/jats:sub>T cells. Our screening strategy includes the identification of<jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>fractions that expand \u03b3<jats:sub>9<\/jats:sub>\u03b4<jats:sub>2<\/jats:sub>T cells with biological functions capable of inhibiting intracellular mycobacterial replication. Chemical treatments of<jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>whole-cell lysates (MtbWL) ruled out protein, nucleic acid, and nonpolar lipids as the<jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>antigens inducing protective \u03b3<jats:sub>9<\/jats:sub>\u03b4<jats:sub>2<\/jats:sub>T cells. Mild acid hydrolysis, which transforms complex carbohydrate to monomeric residues, abrogated the specific activity of<jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>whole-cell lysates, suggesting that a polysaccharide was required for biological activity. Extraction of MtbWL with chloroform-methanol-water (10:10:3) resulted in a polar lipid fraction with highly enriched specific activity; this activity was further enriched by silica gel chromatography. A combination of mass spectrometry and nuclear magnetic resonance analysis of bioactive fractions indicated that 6-<jats:italic>O<\/jats:italic>-methylglucose-containing lipopolysaccharides (mGLP) are predominant components present in this active fraction. These results have important implications for the development of new immunotherapeutic approaches for prevention and treatment of TB.<\/jats:p>","DOI":"10.1128\/iai.01322-15","type":"journal-article","created":{"date-parts":[[2016,6,14]],"date-time":"2016-06-14T02:29:34Z","timestamp":1465871374000},"page":"2449-2462","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":35,"title":["A Subset of Protective \u03b3<sub>9<\/sub>\u03b4<sub>2<\/sub>T Cells Is Activated by Novel Mycobacterial Glycolipid Components"],"prefix":"10.1128","volume":"84","author":[{"given":"Mei","family":"Xia","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Allergy &amp; Immunology, Edward A. 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