{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:45:46Z","timestamp":1790826346316,"version":"4.1.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,10,27]],"date-time":"2016-10-27T00:00:00Z","timestamp":1477526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,10,27]],"date-time":"2016-10-27T00:00:00Z","timestamp":1477526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    CD1 proteins present microbial lipids to T cells. Germline-encoded mycolyl lipid-reactive (GEM) T cells with conserved \u03b1\u03b2 T cell receptors (TCRs) recognize CD1b presenting mycobacterial mycolates. As the molecular basis underpinning TCR recognition of CD1b remains unknown, here we determine the structure of a GEM TCR bound to CD1b presenting glucose-6-\n                    <jats:italic>O<\/jats:italic>\n                    -monomycolate (GMM). The GEM TCR docks centrally above CD1b, whereby the conserved TCR \u03b1-chain extensively contacts CD1b and GMM. Through mutagenesis and study of T cells from tuberculosis patients, we identify a consensus CD1b footprint of TCRs present among GEM T cells. Using both the TCR \u03b1- and \u03b2-chains as tweezers to surround and grip the glucose moiety of GMM, GEM TCRs create a highly specific mechanism for recognizing this mycobacterial glycolipid.\n                  <\/jats:p>","DOI":"10.1038\/ncomms13257","type":"journal-article","created":{"date-parts":[[2016,10,27]],"date-time":"2016-10-27T06:21:40Z","timestamp":1477549300000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["T cell receptor recognition of CD1b presenting a mycobacterial glycolipid"],"prefix":"10.1038","volume":"7","author":[{"given":"Stephanie","family":"Gras","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1446-5701","authenticated-orcid":false,"given":"Ildiko","family":"Van Rhijn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Shahine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tan-Yun","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mugdha","family":"Bhati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Lynn","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanim","family":"Halim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn D.","family":"Tuttle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Gapin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Le Nours","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Branch","family":"Moody","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Rossjohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,10,27]]},"reference":[{"key":"BFncomms13257_CR1","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1111\/imr.12004","volume":"250","author":"L Yin","year":"2012","unstructured":"Yin, L., Scott-Browne, J., Kappler, J. W., Gapin, L. & Marrack, P. T cells and their eons-old obsession with MHC. Immunol. Rev. 250, 49\u201360 (2012).","journal-title":"Immunol. Rev."},{"key":"BFncomms13257_CR2","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1146\/annurev-immunol-032414-112334","volume":"33","author":"J Rossjohn","year":"2015","unstructured":"Rossjohn, J. et al. T cell antigen receptor recognition of antigen-presenting molecules. Annu. Rev. Immunol. 33, 169\u2013200 (2015).","journal-title":"Annu. Rev. Immunol."},{"key":"BFncomms13257_CR3","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1038\/ni.3298","volume":"16","author":"DI Godfrey","year":"2015","unstructured":"Godfrey, D. I., Uldrich, A. P., McCluskey, J., Rossjohn, J. & Moody, D. B. The burgeoning family of unconventional T cells. Nat. Immunol. 16, 1114\u20131123 (2015).","journal-title":"Nat. Immunol."},{"key":"BFncomms13257_CR4","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1038\/nri3889","volume":"15","author":"I Van Rhijn","year":"2015","unstructured":"Van Rhijn, I., Godfrey, D. I., Rossjohn, J. & Moody, D. B. Lipid and small-molecule display by CD1 and MR1. Nat. Rev. Immunol. 15, 643\u2013654 (2015).","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms13257_CR5","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1146\/annurev-immunol-032713-120243","volume":"32","author":"M Salio","year":"2014","unstructured":"Salio, M., Silk, J. D., Jones, E. Y. & Cerundolo, V. Biology of CD1- and MR1-restricted T cells. Annu. Rev. Immunol. 32, 323\u2013366 (2014).","journal-title":"Annu. Rev. Immunol."},{"key":"BFncomms13257_CR6","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1038\/nri1977","volume":"6","author":"SJ Turner","year":"2006","unstructured":"Turner, S. J., Doherty, P. C., McCluskey, J. & Rossjohn, J. Structural determinants of T-cell receptor bias in immunity. Nat. Rev. Immunol. 6, 883\u2013894 (2006).","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms13257_CR7","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.4049\/jimmunol.1500943","volume":"195","author":"I Van Rhijn","year":"2015","unstructured":"Van Rhijn, I. & Moody, D. B. Donor unrestricted T cells: a shared human T cell response. J. Immunol. 195, 1927\u20131932 (2015).","journal-title":"J. Immunol."},{"key":"BFncomms13257_CR8","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1146\/annurev.immunol.25.022106.141711","volume":"25","author":"A Bendelac","year":"2007","unstructured":"Bendelac, A., Savage, P. B. & Teyton, L. The Biology of NKT Cells. Annu. Rev. Immunol. 25, 297\u2013336 (2007).","journal-title":"Annu. Rev. Immunol."},{"key":"BFncomms13257_CR9","doi-asserted-by":"publisher","first-page":"30204","DOI":"10.1074\/jbc.R115.685990","volume":"290","author":"SB Eckle","year":"2015","unstructured":"Eckle, S. B. et al. Recognition of vitamin B Precursors and byproducts by mucosal associated invariant T cells. J. Biol. Chem. 290, 30204\u201330211 (2015).","journal-title":"J. Biol. Chem."},{"key":"BFncomms13257_CR10","doi-asserted-by":"publisher","first-page":"450","DOI":"10.3389\/fimmu.2014.00450","volume":"5","author":"JE Ussher","year":"2014","unstructured":"Ussher, J. E., Klenerman, P. & Willberg, C. B. Mucosal-associated invariant T (MAIT) cells: new players in anti-bacterial immunity. Front. Immunol. 5, 450 (2014).","journal-title":"Front. Immunol."},{"key":"BFncomms13257_CR11","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1146\/annurev.immunol.22.012703.104608","volume":"22","author":"M Brigl","year":"2004","unstructured":"Brigl, M. & Brenner, M. B. CD1: antigen presentation and T Cell function. Annu. Rev. Immunol. 22, 817\u2013890 (2004).","journal-title":"Annu. Rev. Immunol."},{"key":"BFncomms13257_CR12","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1038\/ni948","volume":"4","author":"DM Zajonc","year":"2003","unstructured":"Zajonc, D. M., Elsliger, M. A., Teyton, L. & Wilson, I. A. Crystal structure of CD1a in complex with a sulfatide self antigen at a resolution of 2.15A. Nat. Immunol. 4, 808\u2013815 (2003).","journal-title":"Nat. Immunol."},{"key":"BFncomms13257_CR13","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1038\/ni821","volume":"3","author":"SD Gadola","year":"2002","unstructured":"Gadola, S. D. et al. Structure of human CD1b with bound ligands at 2.3A, a maze for alkyl chains. Nat. Immunol. 3, 721\u2013726 (2002).","journal-title":"Nat. Immunol."},{"key":"BFncomms13257_CR14","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1016\/j.immuni.2010.11.026","volume":"33","author":"L Scharf","year":"2010","unstructured":"Scharf, L. et al. The 2.5A structure of CD1c in complex with a mycobacterial lipid reveals an open groove ideally suited for diverse antigen presentation. Immunity 33, 853\u2013862 (2010).","journal-title":"Immunity"},{"key":"BFncomms13257_CR15","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.coi.2009.05.022","volume":"21","author":"A Kasmar","year":"2009","unstructured":"Kasmar, A., Van Rhijn, I. & Moody, D. B. The evolved functions of CD1 during infection. Curr. Opin. Immunol. 21, 397\u2013403 (2009).","journal-title":"Curr. Opin. Immunol."},{"key":"BFncomms13257_CR16","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1126\/science.273.5273.349","volume":"273","author":"M Sugita","year":"1996","unstructured":"Sugita, M. et al. Cytoplasmic tail-dependent localization of CD1b antigen-presenting molecules to MIICs. Science 273, 349\u2013352 (1996).","journal-title":"Science"},{"key":"BFncomms13257_CR17","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1084\/jem.20110665","volume":"208","author":"AG Kasmar","year":"2011","unstructured":"Kasmar, A. G. et al. CD1b tetramers bind ab T cell receptors to identify a mycobacterial glycolipid-reactive T cell repertoire in humans. J. Exp. Med. 208, 1741\u20131747 (2011).","journal-title":"J. Exp. Med."},{"key":"BFncomms13257_CR18","doi-asserted-by":"publisher","first-page":"4499","DOI":"10.4049\/jimmunol.1301660","volume":"191","author":"AG Kasmar","year":"2013","unstructured":"Kasmar, A. G. et al. Cutting edge: CD1a tetramers and dextramers identify human lipopeptide\u2013specific T cells ex vivo. J. Immunol. 191, 4499\u20134503 (2013).","journal-title":"J. Immunol."},{"key":"BFncomms13257_CR19","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1084\/jem.20120624","volume":"210","author":"D Ly","year":"2013","unstructured":"Ly, D. et al. CD1c tetramers detect ex vivo T cell responses to processed phosphomycoketide antigens. J. Exp. Med. 210, 729\u2013741 (2013).","journal-title":"J. Exp. Med."},{"key":"BFncomms13257_CR20","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1038\/ni.2630","volume":"14","author":"I Van Rhijn","year":"2013","unstructured":"Van Rhijn, I. et al. A conserved human T cell population targets mycobacterial antigens presented by CD1b. Nat. Immunol. 14, 706\u2013713 (2013).","journal-title":"Nat. Immunol."},{"key":"BFncomms13257_CR21","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1111\/imr.12253","volume":"264","author":"I Van Rhijn","year":"2015","unstructured":"Van Rhijn, I. & Moody, D. B. CD1 and mycobacterial lipids activate human T cells. Immunol. Rev. 264, 138\u2013153 (2015).","journal-title":"Immunol. Rev."},{"key":"BFncomms13257_CR22","doi-asserted-by":"publisher","first-page":"4054","DOI":"10.4049\/jimmunol.1400158","volume":"192","author":"I Van Rhijn","year":"2014","unstructured":"Van Rhijn, I. et al. TCR bias and affinity define two compartments of the CD1b\u2013glycolipid-specific T cell repertoire. J. Immunol. 192, 4054\u20134060 (2014).","journal-title":"J. Immunol."},{"key":"BFncomms13257_CR23","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/ni.3098","volume":"16","author":"RW Birkinshaw","year":"2015","unstructured":"Birkinshaw, R. W. et al. [alpha][beta] T cell antigen receptor recognition of CD1a presenting self lipid ligands. Nat. Immunol. 16, 258\u2013266 (2015).","journal-title":"Nat. Immunol."},{"key":"BFncomms13257_CR24","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/nri3328","volume":"12","author":"J Rossjohn","year":"2012","unstructured":"Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L. & Godfrey, D. I. Recognition of CD1d-restricted antigens by natural killer T cells. Nat. Rev. Immunol. 12, 845\u2013857 (2012).","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms13257_CR25","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1038\/ni.2372","volume":"13","author":"O Patel","year":"2012","unstructured":"Patel, O. et al. Recognition of CD1d-sulfatide mediated by a type II natural killer T cell antigen receptor. Nat. Immunol. 13, 857\u2013863 (2012).","journal-title":"Nat. Immunol."},{"key":"BFncomms13257_CR26","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nature05907","volume":"448","author":"NA Borg","year":"2007","unstructured":"Borg, N. A. et al. CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. Nature 448, 44\u201349 (2007).","journal-title":"Nature"},{"key":"BFncomms13257_CR27","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1038\/ni.2371","volume":"13","author":"E Girardi","year":"2012","unstructured":"Girardi, E. et al. Type II natural killer T cells use features of both innate-like and conventional T cells to recognize sulfatide self antigens. Nat. Immunol. 13, 851\u2013856 (2012).","journal-title":"Nat. Immunol."},{"key":"BFncomms13257_CR28","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1126\/science.278.5336.283","volume":"278","author":"DB Moody","year":"1997","unstructured":"Moody, D. B. et al. Structural requirements for glycolipid antigen recognition by CD1b-restricted T cells. Science 278, 283\u2013286 (1997).","journal-title":"Science"},{"key":"BFncomms13257_CR29","doi-asserted-by":"publisher","first-page":"2382","DOI":"10.4049\/jimmunol.172.4.2382","volume":"172","author":"T Batuwangala","year":"2004","unstructured":"Batuwangala, T. et al. The crystal structure of human CD1b with a bound bacterial glycolipid. J. Immunol. 172, 2382\u20132388 (2004).","journal-title":"J. Immunol."},{"key":"BFncomms13257_CR30","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1038\/ni1432","volume":"8","author":"FE Tynan","year":"2007","unstructured":"Tynan, F. E. et al. A T cell receptor flattens a bulged antigenic peptide presented by a major histocompatibility complex class I molecule. Nat. Immunol. 8, 268\u2013276 (2007).","journal-title":"Nat. Immunol."},{"key":"BFncomms13257_CR31","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1084\/jem.189.12.1907","volume":"189","author":"F Tilloy","year":"1999","unstructured":"Tilloy, F. et al. An invariant T cell receptor alpha chain defines a novel TAP-independent major histocompatibility complex class Ib-restricted alpha\/beta T cell subpopulation in mammals. J. Exp. Med. 189, 1907\u20131921 (1999).","journal-title":"J. Exp. Med."},{"key":"BFncomms13257_CR32","doi-asserted-by":"publisher","first-page":"2142","DOI":"10.1038\/ncomms3142","volume":"4","author":"O Patel","year":"2013","unstructured":"Patel, O. et al. Recognition of vitamin B metabolites by mucosal-associated invariant T cells. Nat. Commun. 4, 2142 (2013).","journal-title":"Nat. Commun."},{"key":"BFncomms13257_CR33","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1038\/ni1225","volume":"6","author":"M Koch","year":"2005","unstructured":"Koch, M. et al. The crystal structure of human CD1d with and without alpha-galactosylceramide. Nat. Immunol. 6, 819\u2013826 (2005).","journal-title":"Nat. Immunol."},{"key":"BFncomms13257_CR34","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1084\/jem.192.7.965","volume":"192","author":"DB Moody","year":"2000","unstructured":"Moody, D. B. et al. Cd1b-mediated T cell recognition of a glycolipid antigen generated from mycobacterial lipid and host carbohydrate during infection. J. Exp. Med. 192, 965\u2013976 (2000).","journal-title":"J. Exp. Med."},{"key":"BFncomms13257_CR35","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1107\/S0907444909047337","volume":"66","author":"W Kabsch","year":"2010","unstructured":"Kabsch, W. Xds. Acta. Crystallogr. D Biol. Crystallogr. 66, 125\u2013132 (2010).","journal-title":"Acta. Crystallogr. D Biol. Crystallogr."},{"key":"BFncomms13257_CR36","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1107\/S0907444910045749","volume":"67","author":"MD Winn","year":"2011","unstructured":"Winn, M. D. et al. Overview of the CCP4 suite and current developments. Acta. Crystallogr. D Biol. Crystallogr. 67, 235\u2013242 (2011).","journal-title":"Acta. Crystallogr. D Biol. Crystallogr."},{"key":"BFncomms13257_CR37","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1107\/S0907444910007493","volume":"66","author":"P Emsley","year":"2010","unstructured":"Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta. Crystallogr. D Biol. Crystallogr. 66, 486\u2013501 (2010).","journal-title":"Acta. Crystallogr. D Biol. Crystallogr."},{"key":"BFncomms13257_CR38","unstructured":"Bricogne, G. et al. BUSTER 2.10 edn Global Phasing Ltd (2011)."},{"key":"BFncomms13257_CR39","unstructured":"DeLano, W. L. The PyMOL Molecular Graphics System http:\/\/www.pymol.org (2002)."},{"key":"BFncomms13257_CR40","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/nature13160","volume":"509","author":"AJ Corbett","year":"2014","unstructured":"Corbett, A. J. et al. T-cell activation by transitory neo-antigens derived from distinct microbial pathways. Nature 509, 361\u2013365 (2014).","journal-title":"Nature"},{"key":"BFncomms13257_CR41","doi-asserted-by":"publisher","first-page":"311","DOI":"10.4049\/jimmunol.1102686","volume":"188","author":"S Gras","year":"2012","unstructured":"Gras, S. et al. A structural basis for varied abTCR usage against an immunodominant EBV antigen restricted to a HLA-B8 molecule. J. Immunol. 188, 311\u2013321 (2012).","journal-title":"J. Immunol."},{"key":"BFncomms13257_CR42","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1111\/j.1600-065X.2012.01159.x","volume":"250","author":"S Gras","year":"2012","unstructured":"Gras, S. et al. A structural voyage toward an understanding of the MHC-I-restricted immune response: lessons learned and much to be learned. Immunol. Rev. 250, 61\u201381 (2012).","journal-title":"Immunol. Rev."},{"key":"BFncomms13257_CR43","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.immuni.2009.05.010","volume":"31","author":"T Mallevaey","year":"2009","unstructured":"Mallevaey, T. et al. T cell receptor CDR2 beta and CDR3 beta loops collaborate functionally to shape the iNKT cell repertoire. Immunity 31, 60\u201371 (2009).","journal-title":"Immunity"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms13257.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms13257","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms13257.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T04:49:32Z","timestamp":1672807772000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms13257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,27]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFncomms13257"],"URL":"https:\/\/doi.org\/10.1038\/ncomms13257","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,27]]},"assertion":[{"value":"3 June 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 September 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"13257"}}