Differential recognition of mycobacterium tuberculosis–specific epitopes as a function of tuberculosis disease history

Thomas J. Scriba, Chelsea Carpenter, Sebastian Carrasco Pro, 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, Cecilia S.Lindestam Arlehamn

Research output: Contribution to journalArticlepeer-review

Abstract

Rationale: Individuals 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). Objectives: We 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. Methods: T-cell responses to peptide pools in samples collected from an adult screening and an adolescent validation cohort were measured by IFN-g enzyme-linked immunospot assay or intracellular cytokine staining. Measurements and Main Results: We 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 withou 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 histor sensitive” type 2 epitopes were significantly (P, 0.0001) more homologous to sequences from bacteria found in the human microbiome than type 1 epitopes. Conclusions: Preferential 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.

Original languageEnglish
Pages (from-to)772-781
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume196
Issue number6
DOIs
Publication statusPublished - Sep 15 2017

Keywords

  • Adaptive immunity
  • Microbiome
  • Mycobacterium tuberculosis
  • T-cell epitopes
  • Tuberculosis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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