A mycolic acid-specific CD1-restricted T cell population contributes to acute and memory immune responses in human tuberculosis infection

DJ Montamat-Sicotte, KA Millington, Carrie Willcox, S Hingley-Wilson, S Hackforth, J Innes, OM Kon, David Lammas, David Minnikin, Gurdyal Besra, Benjamin Willcox, A Lalvani

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72 Citations (Scopus)

Abstract

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-Guerin-vaccinated (BCG-vaccinated) controls. These T cells were CD1b restricted, detectable in blood and disease sites, produced both IFN-gamma 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.
Original languageEnglish
Pages (from-to)2493-2503
Number of pages11
JournalJournal of Clinical Investigation
Volume121
Issue number6
DOIs
Publication statusPublished - 1 Jun 2011

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