Major histocompatibility complex class II presenting M72-derived peptides (MHC II-M72)

Major histocompatibility complex class II (MHC II) presenting M72-derived peptides is a molecular complex essential for the induction of protective immunity against Mycobacterium tuberculosis. The M72 antigen is a recombinant fusion protein comprising two immunogenic mycobacterial proteins, Rv1196 (Mtb32A) and Rv0125 (Mtb39A), which are processed by professional antigen-presenting cells and displayed via MHC II molecules to CD4+ T lymphocytes (Gillard et al., 2016, Vaccine). This interaction is the fundamental immunological target of the M72/AS01E vaccine candidate, which has demonstrated significant efficacy in preventing the progression to active pulmonary tuberculosis in individuals with latent infection (Van Der Meeren et al., 2018, NEJM). Upon recognition of the MHC II-peptide complex by the T-cell receptor, CD4+ T cells proliferate and secrete pro-inflammatory cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), which are crucial for activating macrophages to contain the infection (Tait et al., 2019, NEJM). The formation of this complex is a prerequisite for the development of long-term immunological memory against tuberculosis. Consequently, the MHC II-M72 complex serves as a focal point for evaluating vaccine immunogenicity and the correlates of protection in clinical settings (Penn-Nicholson et al., 2020, JCI Insight).

Other names

HLA class II-M72 complexMHC II-Rv1196/Rv0125 complexM72 antigen-MHC II complexMHC class II-M72 peptide complex

The M72/AS01E vaccine delivers the M72 fusion protein, which is internalized by antigen-presenting cells, processed into peptides, and loaded onto MHC class II molecules for presentation to CD4+ T cells, thereby inducing a protective cellular immune response against Mycobacterium tuberculosis (Van Der Meeren et al., 2018, NEJM).