T-cell receptor recognizing M72–MHC class II complexes (M72-specific TCR)

The T-cell receptor (TCR) recognizing M72–MHC class II complexes is a specialized immune receptor that mediates the recognition of the M72 fusion protein, a key component of the M72/AS01E tuberculosis vaccine candidate. M72 is a recombinant protein consisting of two Mycobacterium tuberculosis antigens, Mtb32A (Rv0125) and Mtb39A (Rv1196), which are processed by antigen-presenting cells and displayed on Major Histocompatibility Complex (MHC) class II molecules (Van Der Meeren et al., 2018, NEJM). The binding of this TCR to the M72–MHC II complex is the fundamental step in activating CD4+ T helper cells, which play a central role in the protective immune response against tuberculosis. This interaction, typically enhanced by the AS01E adjuvant system, induces the expansion of polyfunctional memory T cells capable of secreting Th1 cytokines such as interferon-gamma, tumor necrosis factor-alpha, and interleukin-2 (Tait et al., 2019, NEJM). In clinical development, the induction and persistence of T cells bearing these receptors are used as critical indicators of vaccine immunogenicity and protective efficacy against active pulmonary disease (Gillard et al., 2016, Vaccine). While primarily a focus of vaccine research, these receptors represent a specific target for inducing targeted cellular immunity to prevent the progression of latent tuberculosis infection to active disease (Penn-Nicholson et al., 2020, Frontiers in Immunology).

Other names

M72-specific T-cell receptorCD4+ T-cell receptor for M72Mtb32A/Mtb39A-specific T-cell receptorM72-specific TCR

The M72/AS01E vaccine candidate delivers the M72 fusion protein, which is captured by antigen-presenting cells, processed, and presented on MHC class II molecules; the specific T-cell receptor binds this complex, triggering CD4+ T-cell activation, proliferation, and the establishment of protective cytokine-secreting memory cells (Van Der Meeren et al., 2018, NEJM).