CD4+ T-cell receptor complex recognizing Mycobacterium tuberculosis Antigen 85B epitopes (CD4+ TCR-Ag85B)

The CD4+ T-cell receptor (TCR) complex recognizing Mycobacterium tuberculosis Antigen 85B (Ag85B) epitopes is a pivotal mediator of the cellular immune response against tuberculosis (Kaufmann et al., 2014, Nature Reviews Immunology). Ag85B is a major secretory protein and mycolyltransferase (UniProt P9WQP3) essential for the synthesis of the mycobacterial cell wall, making it a highly immunodominant target for the host immune system. The TCR complex on CD4+ T cells specifically recognizes Ag85B-derived peptides when presented by Major Histocompatibility Complex (MHC) class II molecules on the surface of antigen-presenting cells (Woodworth et al., 2014, J Immunol). Upon binding, the TCR complex initiates intracellular signaling cascades that lead to T-cell proliferation and the secretion of Th1-type cytokines, including interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). These cytokines are crucial for the activation of infected macrophages, enabling them to control or eliminate the intracellular M. tuberculosis bacilli. This specific TCR-antigen interaction has been the primary focus of several tuberculosis vaccine candidates, such as MVA85A (McShane et al., 2013, Lancet) and H56:IC31, which aim to boost the frequency and quality of Ag85B-specific T cells. Challenges in targeting this complex include the high degree of HLA polymorphism in human populations, which affects peptide presentation and TCR recognition. Furthermore, chronic exposure to M. tuberculosis can lead to T-cell exhaustion, reducing the functional capacity of the TCR complex to respond to Ag85B. Overall, this TCR complex remains a central target in the global effort to develop more effective immunotherapies and preventative measures against tuberculosis.

Other names

Ag85B-specific T-cell receptorMycobacterium tuberculosis Antigen 85B-specific TCRCD4+ TCR complex (Ag85B)Antigen 85B-specific CD4+ T-cell receptor

Recognition of Ag85B peptides presented by MHC class II molecules on antigen-presenting cells, leading to CD4+ T-cell activation, proliferation, and secretion of pro-inflammatory Th1 cytokines like IFN-gamma and TNF-alpha to control Mycobacterium tuberculosis infection (Kaufmann et al., 2014, Nature Reviews Immunology).