• Thomas J Scriba, Chelsea Carpenter, Pro Sebastian Carrasco SC 2 Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California; and., John Sidney, Munyaradzi Musvosvi, Virginie Rozot, Grégory Seumois, Sandy L Rosales, Pandurangan Vijayanand, Delia Goletti, Edward Makgotlho, Willem Hanekom, Mark Hatherill, Bjoern Peters, Alessandro Sette, and Arlehamn Cecilia S Lindestam CSL 0000-0001-7302-8002 2 Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, Calif.
• 1 South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
• Am. J. Respir. Crit. Care Med. 2017 Sep 15; 196 (6): 772-781.

RationaleIndividuals with a history of tuberculosis (TB) disease are at elevated risk of disease recurrence. The underlying cause is not known, but one explanation is that previous disease results in less-effective immunity against Mycobacterium tuberculosis (Mtb).ObjectivesWe hypothesized that the repertoire of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb infection differs as a function of previous diagnosis of active TB disease.MethodsT-cell responses to peptide pools in samples collected from an adult screening and an adolescent validation cohort were measured by IFN-γ enzyme-linked immunospot assay or intracellular cytokine staining.Measurements And Main ResultsWe identified a set of "type 2" T-cell epitopes that were recognized at 10-fold-lower levels in Mtb-infected individuals with a history of TB disease less than 6 years ago than in those without previous TB. By contrast, "type 1" epitopes were recognized equally well in individuals with or without previous TB. The differential epitope recognition was not due to differences in HLA class II binding, memory phenotypes, or gene expression in the responding T cells. Instead, "TB disease history-sensitive" type 2 epitopes were significantly (P < 0.0001) more homologous to sequences from bacteria found in the human microbiome than type 1 epitopes.ConclusionsPreferential loss of T-cell reactivity to Mtb epitopes that are homologous to bacteria in the microbiome in persons with previous TB disease may reflect long-term effects of antibiotic TB treatment on the microbiome.

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