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

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

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.

Adolescent, Adult, Aged, Aged, 80 and over, Antigens, Bacterial, Child, Child, Preschool, Cohort Studies, Enzyme-Linked Immunospot Assay, Epitopes, T-Lymphocyte, Female, Humans, Infant, Male, Middle Aged, Mycobacterium tuberculosis, Tuberculosis, Young Adult, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
1073-449X
772-781
Scriba, Thomas J.
bd7035c9-67bd-4ffd-8f2d-ada1888aedad
Carpenter, Chelsea
be4c93f3-2c2d-445f-8e75-f4c943d7ea74
Pro, Sebastian Carrasco
0cd75e80-1886-43ec-8d3a-a6c4f89946d9
Sidney, John
ff17bec5-002b-420e-87e2-9b5cfd21ff13
Musvosvi, Munyaradzi
a901824c-16da-4bc1-911c-a17d09b63c4a
Rozot, Virginie
9373fcfa-389f-439b-9ab2-2ac5041d0812
Seumois, Grégory
0be7d3d6-5526-458c-aa5c-cce52410a2ed
Rosales, Sandy L.
04c96f2d-c7af-44e8-83dd-29568d77d40c
Vijayanand, Pandurangan
79514f33-66cf-47cc-a8fa-46bbfc21b7d1
Goletti, Delia
ef3f9a75-ecdb-4878-bce2-c81826fb8e44
Makgotlho, Edward
15741baf-ea9f-4064-a8dd-763183311a16
Hanekom, Willem
c9ec155b-a8ad-49a2-baf2-f8996b43baf9
Hatherill, Mark
b77037e5-e4eb-4883-8474-6237fe7c5f35
Peters, Bjoern
c49863c8-d2c6-4db4-9d2c-72a7c0cbe117
Sette, Alessandro
240988b3-3c05-4041-a39b-8be8e145803c
Arlehamn, Cecilia S. Lindestam
5dac6376-6f50-4e7b-b88b-02b5ec21a7f6
Scriba, Thomas J.
bd7035c9-67bd-4ffd-8f2d-ada1888aedad
Carpenter, Chelsea
be4c93f3-2c2d-445f-8e75-f4c943d7ea74
Pro, Sebastian Carrasco
0cd75e80-1886-43ec-8d3a-a6c4f89946d9
Sidney, John
ff17bec5-002b-420e-87e2-9b5cfd21ff13
Musvosvi, Munyaradzi
a901824c-16da-4bc1-911c-a17d09b63c4a
Rozot, Virginie
9373fcfa-389f-439b-9ab2-2ac5041d0812
Seumois, Grégory
0be7d3d6-5526-458c-aa5c-cce52410a2ed
Rosales, Sandy L.
04c96f2d-c7af-44e8-83dd-29568d77d40c
Vijayanand, Pandurangan
79514f33-66cf-47cc-a8fa-46bbfc21b7d1
Goletti, Delia
ef3f9a75-ecdb-4878-bce2-c81826fb8e44
Makgotlho, Edward
15741baf-ea9f-4064-a8dd-763183311a16
Hanekom, Willem
c9ec155b-a8ad-49a2-baf2-f8996b43baf9
Hatherill, Mark
b77037e5-e4eb-4883-8474-6237fe7c5f35
Peters, Bjoern
c49863c8-d2c6-4db4-9d2c-72a7c0cbe117
Sette, Alessandro
240988b3-3c05-4041-a39b-8be8e145803c
Arlehamn, Cecilia S. Lindestam
5dac6376-6f50-4e7b-b88b-02b5ec21a7f6

Scriba, Thomas J., Carpenter, Chelsea, Pro, Sebastian Carrasco, Sidney, John, Musvosvi, Munyaradzi, Rozot, Virginie, Seumois, Grégory, Rosales, Sandy L., Vijayanand, Pandurangan, Goletti, Delia, Makgotlho, Edward, Hanekom, Willem, Hatherill, Mark, Peters, Bjoern, Sette, Alessandro and Arlehamn, Cecilia S. Lindestam (2017) Differential recognition of mycobacterium tuberculosis-specific epitopes as a function of tuberculosis disease history. American Journal of Respiratory and Critical Care Medicine, 196 (6), 772-781. (doi:10.1164/rccm.201706-1208OC).

Record type: Article

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.

Full text not available from this repository.

More information

Accepted/In Press date: 28 July 2017
e-pub ahead of print date: 31 July 2017
Published date: 15 September 2017
Keywords: Adolescent, Adult, Aged, Aged, 80 and over, Antigens, Bacterial, Child, Child, Preschool, Cohort Studies, Enzyme-Linked Immunospot Assay, Epitopes, T-Lymphocyte, Female, Humans, Infant, Male, Middle Aged, Mycobacterium tuberculosis, Tuberculosis, Young Adult, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 422637
URI: https://eprints.soton.ac.uk/id/eprint/422637
ISSN: 1073-449X
PURE UUID: 5c73d86a-1a08-4cd2-abaf-0665645a63e1

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Date deposited: 27 Jul 2018 16:30
Last modified: 27 Jul 2018 16:30

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Contributors

Author: Thomas J. Scriba
Author: Chelsea Carpenter
Author: Sebastian Carrasco Pro
Author: John Sidney
Author: Munyaradzi Musvosvi
Author: Virginie Rozot
Author: Grégory Seumois
Author: Sandy L. Rosales
Author: Pandurangan Vijayanand
Author: Delia Goletti
Author: Edward Makgotlho
Author: Willem Hanekom
Author: Mark Hatherill
Author: Bjoern Peters
Author: Alessandro Sette
Author: Cecilia S. Lindestam Arlehamn

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