CD4+ T-cell receptor complex specific for Mycobacterium tuberculosis TB10.4 epitopes (TB10.4-specific CD4+ TCR)

The CD4+ T cell TCR complex recognizing Mycobacterium tuberculosis TB10.4 epitopes is a specialized immune receptor that plays a pivotal role in the host defense against tuberculosis. TB10.4, also known as EsxH, is a highly immunogenic protein secreted by the M. tuberculosis Esx-3 type VII secretion system and is a member of the ESAT-6 family. This TCR complex, found on the surface of CD4+ T lymphocytes, specifically recognizes TB10.4-derived peptides, such as the immunodominant 74-88 epitope, when presented by Major Histocompatibility Complex (MHC) Class II molecules on antigen-presenting cells like macrophages. Engagement of the TCR complex triggers intracellular signaling pathways that lead to T-cell proliferation and the secretion of pro-inflammatory Th1 cytokines, including interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). These cytokines are essential for activating the microbicidal functions of macrophages, thereby restricting the growth of M. tuberculosis. Because of its high immunogenicity and role in protective immunity, this TCR complex is a primary target for several candidate tuberculosis vaccines, such as AERAS-402 and H4:IC31, which are designed to expand and maintain a robust population of TB10.4-specific T cells. However, M. tuberculosis has evolved evasion strategies, such as the EsxH-mediated inhibition of the ESCRT machinery, which can impair the presentation of these epitopes and the subsequent activation of the TCR complex.

Other names

EsxH-specific T-cell receptorTB10.4-specific TCRMycobacterium tuberculosis TB10.4-specific CD4+ T-cell receptorCD4/10.4 TCR complex

Antigen-specific activation of T-cell receptors by peptide-MHC Class II complexes, inducing Th1 cytokine secretion (IFN-gamma, TNF-alpha) and macrophage activation to control Mycobacterium tuberculosis replication.