Neoantigen–peptide–major histocompatibility complex (pMHC (peptide–major histocompatibility complex); "neoantigen–pMHC" is commonly used when referring specifically to complexes with neoantigen peptides)

A neoantigen–peptide–major histocompatibility complex (neoantigen–pMHC) is a molecular complex formed when a peptide containing a tumor-specific mutation (neoantigen) is presented by an MHC (major histocompatibility complex) molecule on the surface of a cell. These complexes are critical for T cell–mediated immune recognition in cancer and infectious diseases. The MHC molecule displays the neoantigen peptide in a conformation recognized specifically by T cell receptors (TCRs) on the surface of T lymphocytes, triggering T cell activation and immune attack if the peptide is non-self or altered-self[1][3][4][5][6][7]. Neoantigen–pMHC complexes are central to personalized cancer immunotherapy approaches (e.g., neoantigen vaccines, adoptive T cell transfer), as they enable selective and potent targeting of tumor cells bearing unique mutations while sparing normal tissue. Their immunogenicity depends on the affinity of the peptide for the MHC, the stability of the complex, the specificity of TCR interaction, and the immunological context[1][5]. The biochemical diversity and HLA polymorphism create technical and biological challenges in identifying effective therapeutic targets and predicting patient responses[3][6][7].

Other names

Neoantigen–pMHC complexPeptide–MHC complexMHC–peptide complexMHC–neoantigen complexNeoantigen–MHC complex

Presentation of neoantigen peptide bound to MHC allows recognition by T cell receptor (TCR), mediating selective immune activation against tumor or infected cells[5][6][7]. Drugs or engineered cells targeting pMHC can mediate cytotoxic T cell responses against cells bearing the specific neoantigen, inducing tumor destruction or viral clearance[5][6]. Neoantigen vaccines work by generating or boosting T cell responses against unique tumor-specific pMHC complexes[5].