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

Tumor-associated antigen (TAA) peptide–HLA class I complexes are molecular structures on the surface of tumor cells that present intracellular protein fragments to the immune system. These complexes are formed when degraded cellular proteins are processed by the proteasome, transported into the endoplasmic reticulum, and loaded onto Human Leukocyte Antigen (HLA) class I molecules (Janeway's Immunobiology). In malignant cells, these peptides often originate from mutated proteins (neoantigens), overexpressed self-antigens, or cancer-germline antigens that are not typically expressed in healthy adult tissues (Nature Reviews Cancer). The recognition of these specific peptide-HLA (pHLA) combinations by CD8+ T-cell receptors (TCRs) is a critical step in the adaptive immune response against cancer. Therapeutic interventions, such as TCR-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers like Tebentafusp, are designed to specifically bind these complexes to induce tumor cell lysis (FDA, Kimmtrak). However, the effectiveness of these therapies can be limited by tumor-mediated HLA downregulation and the risk of off-target toxicity if the target peptide sequence is shared by proteins in vital organs (Journal for ImmunoTherapy of Cancer).

Other names

pHLA complexpMHC complexTumor-associated antigen-MHC complexCancer-testis antigen-HLA complexNeoantigen-HLA complexAntigen-presenting complex

Engagement of the peptide-HLA complex by a T-cell receptor (TCR) or TCR-mimetic antibody, leading to the formation of an immunological synapse and subsequent T-cell mediated lysis of the target cell.