CD1b-restricted GEM T cell responses are modulated byMycobacterium tuberculosismycolic acid meromycolate chains

• DOI: 10.1073/pnas.1708252114
• Publication Date: 2017-11-20T19:51:37Z
• Authors: Andrew Chancellor; Anna S. Tocheva; Chris Cave-Ayland; Liku Tezera; Andrew White; Juma’a R. Al Dula...; John S. Bridgeman; Ivo Tews; Susan Wilson; Nikolai M. Lissin; Marc Tebruegge; Ben Marshall; Sally Sharpe; Tim Elliott; Chris-Kriton Skyl...; Jonathan W. Essex; Mark S. Baird; Stephan Gadola; Paul Elkington; Salah Mansour
• Keywords: Models, Molecular; 570; Antigens, Bacterial; Granuloma; T-Lymphocytes; Molecular Conformation; Receptors, Antigen, T-Cell; 610; Gene Expression; Mycobacterium tuberculosis; Lymphocyte Activation; Immunohistochemistry; 3. Good health; Antigens, CD1; 03 medical and health sciences; 0302 clinical medicine; Mycolic Acids; Humans; Tuberculosis; Protein Binding

Significance Tuberculosis is a major global pandemic responsible for more deaths than any other infectious disease, yet no effective vaccine exists. Here, we demonstrate CD1b expression within human tuberculous granulomas, supporting role lipid antigen presentation in host immunity to infection. presents mycolates, the dominant Mycobacterium tuberculosis (Mtb) cell wall class and key virulence factors, αβ T cells. We reveal that mycolate tail moieties, distal head group, are antigenic determinants conserved germline-encoded mycolyl lipid-reactive (GEM) receptors (TCRs). Computational simulations suggest putative mechanism whereby lipid-ligand dynamics regulate GEM-TCR activity. This work provides insights development of histocompatibility complex (MHC)-independent Mtb vaccines, including those target GEM