Major histocompatibility complex–antigen complex on tumor cell (MHC–antigen complex)

Major histocompatibility complex–antigen complexes are cell surface molecular complexes formed when a major histocompatibility complex (either class I or class II) binds a short peptide antigen—derived from intracellular proteins or phagocytosed extracellular proteins—and presents this peptide on the outside of the cell, enabling recognition by T cell receptors on T lymphocytes. On tumor cells, MHC class I–antigen complexes present peptides mainly to cytotoxic CD8+ T cells, which can recognize and kill cancerous cells if the peptides are non-self or tumor-specific. MHC class II–antigen complexes, which may be expressed in some tumor types under inflammatory conditions, interact with CD4+ helper T cells and modulate the immune response. Loss or downregulation of these complexes is a major mechanism of tumor immune escape, and their presence is essential for the effectiveness of many immunotherapies. Targeting tumor-specific MHC–antigen complexes with TCR-based therapeutics, vaccines, or TCR-mimic antibodies is an active area of immuno-oncology research.

Other names

Peptide–MHC complexpMHC complexMHC–peptide complexAntigen–MHC complexMHC-restricted tumor antigen

Facilitate recognition of tumor antigens by T cell receptors (TCR) on cytotoxic (CD8+) T cells (for MHC-I) or helper (CD4+) T cells (for MHC-II), leading to targeted tumor killing or immune activation Enable selection and activation of tumor-reactive T cells Drug mechanisms generally act by enhancing T cell activation against tumor-associated pMHC