Neoantigen–HLA complex

A **neoantigen–HLA complex** is a molecular entity composed of a peptide (neoantigen)—typically a short amino acid sequence containing a mutation unique to tumor or infected cells—bound and presented by a specific class I or II human leukocyte antigen (HLA, also called major histocompatibility complex, MHC) molecule on the cell surface[1][2][3]. Neoantigen–HLA complexes are recognized by T cell receptors (TCRs), enabling antigen-specific immune responses. These complexes are central to the mechanism of action for many next-generation immunotherapies, including TCR-mimic antibodies, bispecific molecules, CAR-T cells, and neoantigen vaccines, enabling selective targeting of diseased cells presenting the mutant peptide in the context of a patient’s HLA molecules[1][2][4]. The structural features of these complexes, including the conformation and solvent-exposed residues of the peptide, are critical determinants of immunogenicity and specificity for therapeutic targeting[1][2][3]. Their therapeutic exploitation is most advanced in cancer, where neoantigens arise from somatic mutations and provide tumor-specific targets largely absent from normal tissues, thus minimizing the risk of autoimmune toxicity. However, challenges include the extreme diversity and patient-specific nature of neoantigens and HLA molecules, and the risk of immune escape via antigen or HLA loss[1][2][3].

Other names

peptide–HLA complexpHLA complexneoantigen–MHC complexpeptide–MHC complex

Blocking or redirecting T cell activation against cells presenting specific neoantigen–HLA complexes Immune cell engagement and directed lysis of target cells presenting the neoantigen–HLA complex Amplification of adaptive immune recognition and killing of tumor or infected cells