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© Clifton E. Barry III, Ph.D., NIAID, NIH.
Colorized scanning electron micrograph of Mycobacterium tuberculosis
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cell reports - 24 Apr 2018

Sayes F, Blanc C, Ates LS, Deboosere N, Orgeur M, Le Chevalier F, Gröschel MI, Frigui W, Song OR, Lo-Man R, Brossier F, Sougakoff W, Bottai D, Brodin P, Charneau P, Brosch R, Majlessi L

Link to Pubmed [PMID] – 29694886

Cell Rep 2018 Apr;23(4):1072-1084

 

 Direct access to fulltext via:

https://www.cell.com/cell-reports/fulltext/S2211-1247(18)30501-1

Abstract

The pathogenic potential of Mycobacterium tuberculosis largely depends on ESX secretion systems exporting members of the multigenic Esx, Esp, and PE/PPE protein families. To study the secretion and regulation patterns of these proteins while circumventing immune cross-reactions due to their extensive sequence homologies, we developed an approach that relies on the recognition of their MHC class II epitopes by highly discriminative T cell receptors (TCRs) of a panel of T cell hybridomas. The latter were engineered so that each expresses a unique fluorescent reporter linked to specific antigen recognition. The resulting polychromatic and multiplexed imaging assay enabled us to measure the secretion of mycobacterial effectors inside infected host cells. We applied this novel technology to a large panel of mutants, clinical isolates, and host-cell types to explore the host-mycobacteria interplay and its impact on the intracellular bacterial secretome, which also revealed the unexpected capacity of phagocytes from lung granuloma to present mycobacterial antigens via MHC class II.