Tumor antigen–major histocompatibility complex complex

The tumor antigen–major histocompatibility complex complex refers to a cell-surface molecular complex comprised of a peptide fragment derived from a tumor-specific (or tumor-associated) antigen bound within the peptide-binding cleft of a major histocompatibility complex (MHC) molecule, typically class I (but sometimes class II). This complex is essential for immune surveillance, as it is recognized by T cell receptors (TCRs) on cytotoxic (CD8+) T cells, which in turn can mediate the destruction of tumor cells displaying the complex. In cancer immunotherapy, therapeutics often aim to enhance the immune system’s ability to recognize and respond to these tumor antigen–MHC complexes, and their presence is a fundamental requirement for most T cell–based therapies. Downregulation or loss of MHC expression is a common mechanism of immune evasion by tumors. The antigen–MHC complex is not a single gene or protein, but a functional unit created by the association of processed tumor antigenic peptides with MHC molecules on the cell surface.

Other names

Tumor antigen–MHC complexpeptide–MHC complexantigen–MHC complextumor peptide–MHC complex

Recognition by T cell receptors (TCRs) on cytotoxic (CD8+) T cells, leading to T cell activation and downstream immune attack on the cell presenting the tumor peptide in the context of the MHC molecule. Initiation of adaptive immune response against tumor antigens. Drugs are designed to either enhance the endogenous T cell response to this complex or provide engineered TCRs to recognize tumor-specific peptide–MHC.