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T cell receptor repertoires associated with control and disease progression following Mycobacterium tuberculosis infection
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T cell receptor repertoires associated with control and disease progression following Mycobacterium tuberculosis infection
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T cell receptor repertoires associated with control and disease progression following Mycobacterium tuberculosis infection
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Journal Article
T cell receptor repertoires associated with control and disease progression following Mycobacterium tuberculosis infection
2023
Overview
Antigen-specific, MHC-restricted αβ T cells are necessary for protective immunity against
Mycobacterium tuberculosis
, but the ability to broadly study these responses has been limited. In the present study, we used single-cell and bulk T cell receptor (TCR) sequencing and the GLIPH2 algorithm to analyze
M. tuberculosis
-specific sequences in two longitudinal cohorts, comprising 166 individuals with
M. tuberculosis
infection who progressed to either tuberculosis (
n
= 48) or controlled infection (
n
= 118). We found 24 T cell groups with similar TCR-β sequences, predicted by GLIPH2 to have common TCR specificities, which were associated with control of infection (
n
= 17), and others that were associated with progression to disease (
n
= 7). Using a genome-wide
M. tuberculosis
antigen screen, we identified peptides targeted by T cell similarity groups enriched either in controllers or in progressors. We propose that antigens recognized by T cell similarity groups associated with control of infection can be considered as high-priority targets for future vaccine development.
Analysis of peripheral mycobacteria-reactive CD4
+
T cell receptor sequences from individuals infected with
Mycobacterium
tuberculosis
shows a high degree of overlap between progressors and controllers, but points to some distinct clonotypes that are enriched in either group.
Publisher
Nature Publishing Group US,Nature Publishing Group
