Mycobacterium tuberculosis antigen TB10.4-specific T-cell receptor (TB10.4-specific TCR) (TB10.4-specific TCR)

Mycobacterium tuberculosis antigen TB10.4-specific T-cell receptors (TCRs) are specialized protein complexes on the surface of T lymphocytes that recognize the TB10.4 (also known as EsxH) protein. TB10.4 is a highly immunodominant antigen secreted by the Mycobacterium tuberculosis Esx-3 secretion system and is a primary target of the host's cellular immune response during infection (PubMed: 21646655). These receptors function by binding to specific TB10.4 peptide fragments presented by Major Histocompatibility Complex (MHC) molecules on infected macrophages, which triggers T-cell activation and the production of protective cytokines such as interferon-gamma and tumor necrosis factor-alpha (PubMed: 25332163). In therapeutic development, these TCRs are the primary targets for several subunit vaccines, most notably H4:IC31 (AERAS-404), which aims to expand the population of TB10.4-specific T cells to provide long-term immunity (PubMed: 21835174). Additionally, they are being explored in the context of adoptive T-cell therapies, where T cells are engineered to express high-affinity TB10.4-specific TCRs to treat multi-drug resistant tuberculosis (PubMed: 30045925). Understanding the structural basis of this TCR-antigen interaction is crucial for overcoming challenges related to HLA polymorphism and ensuring broad vaccine efficacy across diverse human populations.

Other names

EsxH-specific T-cell receptorTB10.4-specific TCRMycobacterium tuberculosis TB10.4-specific TCR

Recognition of TB10.4 (EsxH) peptide fragments presented by Major Histocompatibility Complex (MHC) molecules on the surface of infected cells, leading to T-cell activation and the release of effector molecules to control Mycobacterium tuberculosis infection.