Human leukocyte antigen A*02:01 presenting tumor-associated antigen-derived neoepitopes (HLA-A*02:01/TAA-neoepitope complex)

Human leukocyte antigen A*02:01 (HLA-A*02:01) presenting tumor-associated antigen (TAA)-derived neoepitopes is a critical molecular complex used by the immune system to identify and eliminate malignant cells (UniProt: P01892). HLA-A*02:01 is a Class I Major Histocompatibility Complex (MHC) protein that displays intracellularly derived peptides on the cell surface for recognition by CD8+ T-cell receptors (TCRs). In the context of oncology, these peptides may originate from mutated proteins (neoantigens) or aberrantly expressed self-proteins (TAAs), creating a unique signature for immunotherapy (Nature Medicine, 2019). Therapeutic interventions, such as TCR-engineered T-cells (TCR-T) like Afamitresgene autoleucel and Immune mobilizing monoclonal TCRs Against Cancer (ImmTACs) like Tebentafusp, are designed to bind these specific peptide-HLA complexes with high affinity (FDA, 2022; NEJM, 2022). This targeting mechanism allows for the destruction of tumor cells that may lack traditional surface markers but express internal oncogenic proteins. However, successful treatment requires patients to be HLA-A*02:01 positive and the tumor to maintain antigen presentation, as HLA downregulation or loss of heterozygosity are common mechanisms of immune evasion (Cancer Discovery, 2021).

Other names

HLA-A2/peptide complexMHC-I/neoantigen complexHLA-A*02:01-restricted tumor neoantigenpMHC complexHLA-A*02:01/peptide-MHC

Recognition of specific peptide-MHC complexes by engineered T-cell receptors (TCRs) or TCR-like antibodies to induce T-cell mediated cytotoxicity against cells displaying the target neoepitope.