Tumor-associated peptide-major histocompatibility complex class I (pMHC-I) (pMHC-I)

Tumor-associated peptide-major histocompatibility complex class I (pMHC-I) complexes are the fundamental targets for CD8+ T-cell-mediated immunity in cancer. These complexes consist of an 8-11 amino acid peptide, derived from intracellular tumor antigens such as neoantigens or cancer-testis antigens, nested within the binding groove of an MHC class I molecule on the tumor cell surface. Recognition of these complexes by the T-cell receptors (TCRs) of infused tumor-infiltrating lymphocytes (TILs) or engineered TCR-T cells triggers a cytotoxic cascade, including the release of perforins and granzymes, leading to tumor cell apoptosis. This interaction is highly specific to both the peptide sequence and the patient's human leukocyte antigen (HLA) type, necessitating precise patient selection. While highly effective in inducing durable responses in solid tumors like melanoma, therapeutic challenges include immune escape through HLA downregulation and potential on-target, off-tumor toxicities if the target peptide is also presented by healthy tissues.

Other names

Tumor antigen-MHC complexHLA-peptide complexNeoantigen-MHC complexCancer-germline antigen-MHC complexpMHC-I complexTumor-specific peptide-MHC

Recognition by T-cell receptors (TCRs) on CD8+ T cells leads to the formation of an immunological synapse, activation of the TCR-CD3 complex, and subsequent release of perforin and granzymes to induce tumor cell apoptosis.