Tumor-associated antigen peptide-Major Histocompatibility Complex (TAA-pMHC) (TAA-pMHC)

Tumor-associated antigen peptide-Major Histocompatibility Complexes (TAA-pMHC) are the fundamental targets for cellular immunity, consisting of short peptide fragments derived from intracellular proteins displayed on the cell surface by MHC molecules (Murphy & Weaver, Janeway's Immunobiology, 2016). This target class is highly significant in oncology because it allows the immune system to detect intracellular proteins, including mutated neoantigens or overexpressed self-antigens, which are inaccessible to traditional antibody-based therapies (Klaeger et al., Cancer Cell, 2021). Therapeutic interventions such as TCR-engineered T-cells (TCR-T) and TCR-bispecific molecules are designed to recognize these specific pMHC targets with high affinity and specificity (Walseng et al., Immunotherapy, 2017). For example, the drug tebentafusp targets a gp100-derived peptide presented by HLA-A*02:01 to treat metastatic uveal melanoma (Nathan et al., NEJM, 2021). A critical requirement for these therapies is the patient's expression of a specific HLA allele, a constraint known as HLA restriction (Rock et al., Trends in Immunology, 2016). Safety considerations are paramount, as engineered TCRs must avoid cross-reactivity with similar peptides in healthy tissues to prevent severe off-target toxicities (Linette et al., Blood, 2013).

Other names

Peptide-Major Histocompatibility ComplexpMHC complexHLA-peptide complexTumor antigen-MHC complexAntigen-presenting complex

T-cell receptor-mediated recognition of peptide-MHC complexes leading to T-cell activation and cytotoxic tumor cell lysis.