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Am J Respir Crit Care Med. 2017 Sep 15;196(6):772-781. doi: 10.1164/rccm.201706-1208OC.

Differential Recognition of Mycobacterium tuberculosis-Specific Epitopes as a Function of Tuberculosis Disease History.

Author information

1
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.
2
2 Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California; and.
3
3 Translational Research Unit, Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases, Rome, Italy.

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-γ 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 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.

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.

KEYWORDS:

Mycobacterium tuberculosis; T-cell epitopes; adaptive immunity; microbiome; tuberculosis

PMID:
28759253
PMCID:
PMC5620682
DOI:
10.1164/rccm.201706-1208OC
[Indexed for MEDLINE]
Free PMC Article

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