Mycobacterium tuberculosis-specific CD4+ and CD8+ T cell (recognizing Ag85B and TB10.4) (Mtb-specific T cells (Ag85B/TB10.4))

Mycobacterium tuberculosis-specific CD4+ and CD8+ T cells recognizing Ag85B and TB10.4 epitopes are specialized immune effectors central to the control of Mycobacterium tuberculosis (Mtb) infection. Ag85B (UniProt P9WQP3) is a secreted mycolyltransferase essential for cell wall integrity, while TB10.4 (EsxH, UniProt P9WNK3) is a potent T-cell antigen involved in metal homeostasis and virulence. These T cells are the primary biological targets of the H4:IC31 (AERAS-404) subunit vaccine, which consists of an Ag85B-TB10.4 fusion protein formulated with the IC31 adjuvant (Geldenhuys et al., 2015). Upon activation, CD4+ T cells produce critical Th1 cytokines, including interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), which are necessary for macrophage-mediated killing of intracellular Mtb (Kaufmann, 2010). CD8+ T cells contribute to protection through the secretion of cytokines and the direct lysis of infected host cells via perforin and granzyme pathways. Monitoring the frequency and polyfunctionality of these T cell populations serves as a key correlate of immunogenicity in clinical trials for tuberculosis vaccines.

Other names

Ag85B/TB10.4-specific T cellsH4-specific T cellsAntigen 85B and TB10.4 reactive T lymphocytesMtb-specific CD4+ and CD8+ T cells

Vaccines containing the Ag85B and TB10.4 fusion protein (H4) induce the expansion of memory CD4+ and CD8+ T cells that recognize these antigens on the surface of Mtb-infected macrophages via MHC molecules, leading to macrophage activation and bacterial clearance.