Tumor-associated peptide–Major Histocompatibility Complex class I (pHLA-I) complex (pHLA-I)

Tumor-associated peptide–HLA class I complexes are molecular assemblies consisting of a short peptide fragment derived from a tumor-associated antigen (TAA) or neoantigen bound to a Major Histocompatibility Complex (MHC) class I molecule. These complexes are presented on the surface of endogenous antigen-presenting cells (APCs) and tumor cells, serving as the primary signal for recognition by CD8+ cytotoxic T lymphocytes (Nature Reviews Immunology, 2022). In the context of immunotherapy, these complexes are targeted by T-cell receptor (TCR) engineered T-cells, TCR-mimetic antibodies, and bispecific T-cell engagers to induce a specific immune response against malignant cells (The Lancet, 2024). The specificity of the interaction depends on both the particular HLA allele and the unique amino acid sequence of the presented peptide. Targeting these complexes allows for the recognition of intracellular proteins that are otherwise inaccessible to traditional antibody-based therapies (Frontiers in Immunology, 2021). However, challenges include the high polymorphism of HLA genes and the potential for tumor cells to downregulate HLA expression to escape immune detection (Journal for ImmunoTherapy of Cancer, 2020).

Other names

Peptide-MHC class I complexpMHC-ITumor-specific peptide-HLA complexHLA-restricted tumor antigenAntigen-presenting cell pHLA complex

T-cell receptor (TCR) binding and subsequent activation of cytotoxic T-cell signaling pathways leading to target cell lysis.