T-cell receptor recognizing Ag85B-ESAT-6-derived peptide presented by MHC (TCR-Ag85B-ESAT-6)

The T-cell receptor (TCR) recognizing the Ag85B-ESAT-6-derived peptide is a specialized immune receptor essential for the adaptive defense against Mycobacterium tuberculosis. This TCR specifically identifies a fusion of two immunodominant mycobacterial antigens: Antigen 85B (Ag85B), a mycolyltransferase involved in cell wall synthesis, and Early Secretory Antigenic Target-6 (ESAT-6), a potent virulence factor [Andersen et al., 2007]. When these antigens are processed and presented by Major Histocompatibility Complex (MHC) molecules—typically MHC Class II on the surface of antigen-presenting cells—the TCR binds to the complex, initiating a signaling cascade that activates the T cell. This activation is a cornerstone of the Th1 immune response, characterized by the production of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), which are vital for activating macrophages to contain or eliminate the bacteria [Sia et al., 2015]. In clinical development, this TCR is the primary focus of subunit vaccines such as H1 and H56, which are designed to boost the frequency and efficacy of T cells carrying this receptor to prevent or treat tuberculosis [Lindenstrøm et al., 2009]. Beyond vaccines, this TCR-peptide-MHC interaction serves as the basis for diagnostic tools like Interferon-Gamma Release Assays (IGRAs), which detect latent or active infection by measuring the response of these specific T cells to the antigens. Therapeutic strategies targeting this TCR aim to enhance protective immunity while avoiding excessive inflammation that could lead to tissue damage [Brookes et al., 2003].

Other names

Ag85B-ESAT-6 specific T-cell receptorH1-specific T-cell receptorESAT-6/Ag85B-reactive T-cell receptorMycobacterium tuberculosis antigen-specific TCR

The TCR recognizes specific mycobacterial peptides (Ag85B and ESAT-6) presented by MHC molecules, triggering T-cell activation, proliferation, and the secretion of Th1 cytokines like IFN-gamma and TNF-alpha to facilitate the killing of intracellular Mycobacterium tuberculosis [Dietrich et al., 2006].