Tumor-associated and neoantigen peptide-MHC class II complex (pMHC-II)

Tumor-associated and neoantigen peptide-MHC class II complexes are molecular assemblies on the surface of tumor cells and antigen-presenting cells (APCs) that present degraded protein fragments to the immune system (Schumacher & Schreiber, Science, 2015). These complexes consist of a peptide derived from tumor-specific mutations (neoantigens) or overexpressed proteins (tumor-associated antigens) bound to Major Histocompatibility Complex (MHC) class II molecules, such as HLA-DR, HLA-DQ, or HLA-DP (Axelrod et al., JCI, 2019). While MHC class II expression was historically thought to be restricted to professional APCs, it is now recognized that many solid tumors express these complexes to interact directly with CD4+ T cells (Hailemichael et al., Nature Medicine, 2013). Recognition of these pMHC-II complexes by CD4+ T-cell receptors (TCRs) is vital for the induction of a comprehensive anti-tumor immune response, including cytokine production and the enhancement of CD8+ T-cell activity (Kennedy & Celis, Immunol Rev, 2008). Therapeutic interventions targeting these complexes include personalized neoantigen vaccines, TCR-engineered T-cell (TCR-T) therapies, and bispecific antibodies (Ott et al., Nature, 2017). Challenges in targeting these complexes include the extreme polymorphism of the HLA system and the potential for tumor cells to downregulate MHC expression as a mechanism of immune evasion (Garrido et al., Cancer Immunol Immunother, 2016).

Other names

Peptide-MHC class II complexpHLA-II complexTumor-specific MHC-II-restricted antigenNeoantigen-HLA class II complexTumor-associated antigen-MHC class II complex

Recognition of the peptide-MHC complex by the T-cell receptor (TCR) on CD4+ T lymphocytes, leading to T-cell activation, cytokine secretion (e.g., IFN-gamma), and coordination of the adaptive immune response against tumor cells.