Dissemin is shutting down on January 1st, 2025

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National Academy of Sciences, Proceedings of the National Academy of Sciences, 51(114), 2017

DOI: 10.1073/pnas.1708252114

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

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

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 a role for CD1b lipid antigen presentation in host immunity to infection. CD1b presents mycolates, the dominant Mycobacterium tuberculosis (Mtb) cell wall lipid class and key virulence factors, to αβ T cells. We reveal that mycolate tail moieties, distal to the head group, are antigenic determinants for the conserved human germline-encoded mycolyl lipid-reactive (GEM) T cell receptors (TCRs). Computational simulations suggest a putative mechanism whereby lipid-ligand dynamics within CD1b regulate GEM-TCR activity. This work provides insights for the development of major histocompatibility complex (MHC)-independent Mtb lipid vaccines, including those that target GEM T cells.