Current tuberculosis (TB) vaccine strategies are largely aimed at activating conventional T cell responses to mycobacterial protein antigens. However, the lipid-rich cell wall of Mycobacterium tuberculosis (M. tuberculosis) is essential for pathogenicity and provides targets for unconventional T cell recognition. Group 1 CD1–restricted T cells recognize mycobacterial lipids, but their function in human TB is unclear and their ability to establish memory is unknown. Here, we characterized T cells specific for mycolic acid (MA), the predominant mycobacterial cell wall lipid and key virulence factor, in patients with active TB infection. MA-specific T cells were predominant in TB patients at diagnosis, but were absent in uninfected bacillus Calmette-Guérin–vaccinated (BCG-vaccinated) controls. These T cells were CD1b restricted, detectable in blood and disease sites, produced both IFN-γ and IL-2, and exhibited effector and central memory phenotypes. MA-specific responses contracted markedly with declining pathogen burden and, in patients followed longitudinally, exhibited recall expansion upon antigen reencounter in vitro long after successful treatment, indicative of lipid-specific immunological memory. T cell recognition of MA is therefore a significant component of the acute adaptive and memory immune response in TB, suggesting that mycobacterial lipids may be promising targets for improved TB vaccines.
Damien J. Montamat-Sicotte, Kerry A. Millington, Carrie R. Willcox, Suzie Hingley-Wilson, Sarah Hackforth, John Innes, Onn Min Kon, David A. Lammas, David E. Minnikin, Gurdyal S. Besra, Benjamin E. Willcox, Ajit Lalvani
Title and authors | Publication | Year |
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The T-Cell Response to Lipid Antigens of Mycobacterium tuberculosis
GD Libero, L Mori |
Frontiers in immunology | 2014 |
A polymorphism in human CD1A is associated with susceptibility to tuberculosis
C Seshadri, NT Thuong, NT Yen, ND Bang, TT Chau, GE Thwaites, SJ Dunstan, TR Hawn |
Genes and Immunity | 2014 |
A novel self-lipid antigen targets human T cells against CD1c(+) leukemias
M Lepore, C Lalla, SR Gundimeda, H Gsellinger, M Consonni, C Garavaglia, S Sansano, F Piccolo, A Scelfo, D Häussinger, D Montagna, F Locatelli, C Bonini, A Bondanza, A Forcina, Z Li, G Ni, F Ciceri, P Jenö, C Xia, L Mori, P Dellabona, G Casorati, GD Libero |
Journal of Experimental Medicine | 2014 |
Protective Effect of a Lipid-Based Preparation from Mycobacterium smegmatis in a Murine Model of Progressive Pulmonary Tuberculosis
MA los García, R Borrero, ME Lanio, Y Tirado, N Alvarez, A Puig, A Aguilar, L Canet, DM Espinoza, JB Payán, ME Sarmiento, R Hernández-Pando, MN Norazmi, A Acosta |
BioMed Research International | 2014 |
Targeted Delivery of Mycobacterial Antigens to Human Dendritic Cells via Siglec-7 Induces Robust T Cell Activation
N Kawasaki, CD Rillahan, TY Cheng, IV Rhijn, MS Macauley, DB Moody, JC Paulson |
Journal of immunology (Baltimore, Md. : 1950) | 2014 |
Nonclassical T Cells and Their Antigens in Tuberculosis
GD Libero, A Singhal, M Lepore, L Mori |
Cold Spring Harbor Perspectives in Medicine | 2014 |