T cell receptor recognition of CD1b presenting a mycobacterial glycolipid

• Published in: Nature communications 2016-10, Vol.7 (1), p.13257-13257, Article 13257
• Main Authors: Gras, Stephanie, Van Rhijn, Ildiko, Shahine, Adam, Cheng, Tan-Yun, Bhati, Mugdha, Tan, Li Lynn, Halim, Hanim, Tuttle, Kathryn D., Gapin, Laurent, Le Nours, Jérôme, Moody, D. Branch, Rossjohn, Jamie
• Format: Article
• Language: English
• Subjects: 631/250/1619/554/1775; 631/250/21/1293; 631/250/2152/1566/20; 631/45/535/1266; Antigens; Antigens, CD1 - metabolism; Cloning; Data collection; Glucose; Glycolipids - immunology; Histocompatibility Antigens Class I - metabolism; Humanities and Social Sciences; Humans; Immunology; Latent Tuberculosis - immunology; Lipids; Lymphocytes; Minor Histocompatibility Antigens - metabolism; multidisciplinary; Mycobacterium phlei; Protein Conformation; Proteins; Receptors, Antigen, T-Cell - metabolism; Rhodococcus equi; Science; Science (multidisciplinary); T cell receptors; T-Lymphocytes - immunology; Tuberculosis
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms13257

CD1 proteins present microbial lipids to T cells. Germline-encoded mycolyl lipid-reactive (GEM) T cells with conserved αβ 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- O -monomycolate (GMM). The GEM TCR docks centrally above CD1b, whereby the conserved TCR α-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 α- and β-chains as tweezers to surround and grip the glucose moiety of GMM, GEM TCRs create a highly specific mechanism for recognizing this mycobacterial glycolipid. Germline-encoded mycolyl lipid-reactive (GEM) T cells recognize CD1b proteins presenting mycobacterial mycolates via their T-cell receptors (TCRs). Here, the authors present the structure of this interaction and provide a molecular basis for the co-recognition of CD1b and a mycobacterial glycolipid.