{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T23:40:08Z","timestamp":1742946008586,"version":"3.40.3"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"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":[[2013,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Most vaccines and basic studies of T cell epitopes in Mycobacterium tuberculosis emphasize water-soluble proteins that are secreted into the extracellular space and presented in the context of MHC class II. Much less is known about the role of Ags retained within the cell wall. We used polyclonal T cells from infected humans to probe for responses to immunodominant Ags in the M. tuberculosis cell wall. We found that the magnitude of response to secreted or cell wall intrinsic compounds was similar among healthy controls, patients with latent tuberculosis, and patients with active tuberculosis. Individual responses to secreted Ags and cell wall extract were strongly correlated (r2 = 0.495, p = 0.001), suggesting that T cells responding to cell wall and secreted Ags are present at similar frequency. Surprisingly, T cell stimulatory factors intrinsic to the cell wall partition into organic solvents; however, these responses are not explained by CD1-mediated presentation of lipids. Instead, we find that molecules soluble in organic solvents are dependent upon MHC class II and recognized by IFN-\u03b3\u2013secreting CD4+ T cells. We reasoned that MHC class II\u2013dependent Ags extracting into lipid mixtures might be found among triacylated lipoproteins present in mycobacteria. We used M. tuberculosis lacking prolipoprotein signal peptidase A (lspA), an enzyme required for lipoprotein synthesis, to demonstrate loss of polyclonal T cell responses. Our results demonstrate the use of bacterial genetics to identify lipoproteins as an unexpected and immunodominant class of cell wall\u2013associated Ags targeted by the polyclonal human T cell response to M. tuberculosis.<\/jats:p>","DOI":"10.4049\/jimmunol.1201667","type":"journal-article","created":{"date-parts":[[2012,11,30]],"date-time":"2012-11-30T01:25:41Z","timestamp":1354238741000},"page":"278-284","source":"Crossref","is-referenced-by-count":15,"title":["Lipoproteins Are Major Targets of the Polyclonal Human T Cell Response to <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.1093","volume":"190","author":[{"given":"Chetan","family":"Seshadri","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Brigham and Women\u2019s Hospital , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie T","family":"Turner","sequence":"additional","affiliation":[{"name":"Tuberculosis Treatment Unit, Lemuel Shattuck Hospital , Jamaica Plain, MA 02130"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M","family":"Lewinsohn","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Portland Veteran Affairs Medical Center , Portland, OR 97239"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ildiko","family":"Van Rhijn","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Brigham and Women\u2019s Hospital , Boston, MA 02115"},{"name":"Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University , 3584 CL Utrecht,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,1,1]]},"reference":[{"key":"2025032406190180200_r1","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1111\/j.1600-065X.2008.00693.x","article-title":"Early T-cell responses in tuberculosis immunity","volume":"225","author":"Winslow","year":"2008","journal-title":"Immunol. 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