Tumor-associated antigen–derived peptide–HLA class I complex (TAA-peptide-HLA-I)

Tumor-associated antigen (TAA)-derived peptide–HLA class I complexes are essential molecular assemblies on the cell surface that present fragments of intracellular proteins to CD8+ T cells (PMID: 31110075). These complexes consist of a polymorphic HLA class I heavy chain, a beta-2 microglobulin subunit, and a short peptide (typically 8-11 amino acids) derived from tumor-specific or tumor-associated proteins (PMID: 29305541). They function as the primary recognition unit for the adaptive immune system to identify and eliminate malignant cells via T-cell receptor (TCR) binding (PMID: 32661138). In modern immunotherapy, these complexes are targeted by TCR-engineered T-cells, bispecific molecules like Tebentafusp, and cancer vaccines to induce potent anti-tumor activity (PMID: 34551229). Because these targets represent the presentation of intracellular oncogenic drivers, they allow for the therapeutic targeting of proteins that are otherwise inaccessible to traditional antibody-based therapies (PMID: 38543331). However, clinical application is often restricted to specific patient HLA genotypes and carries the risk of severe off-target toxicity if the targeted peptide sequence is shared with proteins in vital healthy tissues (PMID: 23856024).

Other names

pHLA complexpMHC class IMHC-I-peptide complexTumor antigen-MHC complexPeptide-MHC complexAntigen-presenting complex

Direct binding by T-cell receptors (TCRs) or TCR-mimetic antibodies, which facilitates the formation of an immunological synapse and triggers cytotoxic T-lymphocyte (CTL) mediated killing of the target cell.