Human memory CD4⁺ T-cells recognize <i>Mycobacterium tuberculosis</i>-infected macrophages amid broader pathogen-specific responses.

ABSTRACT: Recognition of macrophages infected with Mycobacterium tuberculosis (Mtb) is essential for CD4⁺ T cells to prevent tuberculosis (TB). Yet not all antigen-specific T cells recognize infected macrophages in human and murine models. Using monocyte-derived macrophages (MDMs) and autologous memory CD4⁺ T cells from individuals with latent Mtb infection (LTBI), we quantify T cell activation in response to infected macrophages. T cell antigen receptor (TCR) sequencing revealed >70% of unique and >90% of total Mtb-specific TCR clonotypes in stable LTBI are linked to recognition of infected macrophages, while a subset required exogenous antigen exposure, suggesting incomplete recognition. Clonotypes specific for multiple Mtb antigens and other pathogens were identified,

SUBMITTER: Stetsenko V 

PROVIDER: S-EPMC11888249 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature