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In humans, <jats:italic>M. tuberculosis<\/jats:italic> reactive CD8 T\u00a0cells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 T\u00a0cells recognizing <jats:italic>M. tuberculosis<\/jats:italic> Ags presented by nonclassical MHC class Ib molecules. We show here that CD8 T\u00a0cells from tuberculosis (TB) patients recognize HLA\u2010E\u2010binding <jats:italic>M. tuberculosis<\/jats:italic> peptides in a CD3\/TCR \u03b1\u03b2 mediated and CD8\u2010dependent manner, and represent an additional type of effector cells playing a role in immune response to <jats:italic>M. tuberculosis<\/jats:italic> during active infection. HLA\u2010E\u2010restricted recognition of <jats:italic>M. tuberculosis<\/jats:italic> peptides is detectable by a significant enhanced ex vivo frequency of tetramer\u2010specific circulating CD8 T\u00a0cells during active TB. These CD8 T\u00a0cells produce type 2 cytokines upon antigenic in vitro stimulation, help B cells for Ab production, and mediate limited TRAIL\u2010dependent cytolytic and microbicidal activity toward <jats:italic>M. tuberculosis<\/jats:italic> infected target cells. Our results, together with the finding that HLA\u2010E\/<jats:italic>M. tuberculosis<\/jats:italic> peptide specific CD8 T\u00a0cells are detected in TB patients with or without HIV coinfection, suggest that this is a new human T\u2010cell population that participates in immune response in TB.<\/jats:p>","DOI":"10.1002\/eji.201445193","type":"journal-article","created":{"date-parts":[[2015,1,29]],"date-time":"2015-01-29T06:27:20Z","timestamp":1422512840000},"page":"1069-1081","source":"Crossref","is-referenced-by-count":65,"title":["Human CD8 T lymphocytes recognize <i>Mycobacterium tuberculosis<\/i> antigens presented by HLA\u2010E during active tuberculosis and express type 2 cytokines"],"prefix":"10.1002","volume":"45","author":[{"given":"Nadia","family":"Caccamo","sequence":"first","affiliation":[{"name":"Central Laboratory for Advanced Diagnostic and Biomedical Research (CLADIBIOR) Universit\u00e0 di Palermo  Palermo Italy"},{"name":"Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi  Palermo Italy"}]},{"given":"Gabriella","family":"Pietra","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine University of Genova  Genova Italy"},{"name":"IRCCS AOU San Martino\u2010IST  Genova Italy"}]},{"given":"Lucy C.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Melbourne  Parkville Australia"}]},{"given":"Andrew G.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Melbourne  Parkville Australia"}]},{"given":"Teresa","family":"Prezzemolo","sequence":"additional","affiliation":[{"name":"Central Laboratory for Advanced Diagnostic and Biomedical Research (CLADIBIOR) Universit\u00e0 di Palermo  Palermo Italy"},{"name":"Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi  Palermo Italy"}]},{"given":"Marco P.","family":"La Manna","sequence":"additional","affiliation":[{"name":"Central Laboratory for Advanced Diagnostic and Biomedical Research (CLADIBIOR) Universit\u00e0 di Palermo  Palermo Italy"},{"name":"Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi  Palermo Italy"}]},{"given":"Diana","family":"Di\u00a0Liberto","sequence":"additional","affiliation":[{"name":"Central Laboratory for Advanced Diagnostic and Biomedical Research (CLADIBIOR) Universit\u00e0 di Palermo  Palermo Italy"},{"name":"Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi  Palermo Italy"}]},{"given":"Simone A.","family":"Joosten","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Leiden University Medical Center  Leiden The Netherlands"}]},{"given":"Krista E.","family":"van Meijgaarden","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Leiden University Medical Center  Leiden The Netherlands"}]},{"given":"Paola","family":"Di Carlo","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Clinica e delle Patologie Emergenti Universit\u00e0 di Palermo  Palermo Italy"}]},{"given":"Lucina","family":"Titone","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Clinica e delle Patologie Emergenti Universit\u00e0 di Palermo  Palermo Italy"}]},{"given":"Lorenzo","family":"Moretta","sequence":"additional","affiliation":[{"name":"Istituto Giannina Gaslini  Genova Italy"}]},{"given":"Maria C.","family":"Mingari","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine University of Genova  Genova Italy"},{"name":"IRCCS AOU San Martino\u2010IST  Genova Italy"}]},{"given":"Tom H. M.","family":"Ottenhoff","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Leiden University Medical Center  Leiden The Netherlands"}]},{"given":"Francesco","family":"Dieli","sequence":"additional","affiliation":[{"name":"Central Laboratory for Advanced Diagnostic and Biomedical Research (CLADIBIOR) Universit\u00e0 di Palermo  Palermo Italy"},{"name":"Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi  Palermo Italy"}]}],"member":"311","published-online":{"date-parts":[[2015,2,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002607"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-095939"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2012.06.002"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.24.12013"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5319.1684"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"366","DOI":"10.4049\/jimmunol.162.1.366","article-title":"CD1\u2010restricted microbial lipid antigen\u2010specific recognition found in the CD8+ \u00a0\u03b1\u03b2 T cell pool","volume":"162","author":"Rosat J. 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