Human leukocyte antigen A*02-presented tumor-associated antigen peptide (HLA-A*02/TAA peptide)

Human leukocyte antigen A*02 (HLA-A*02)-presented tumor-associated antigen (TAA) peptides are molecular complexes consisting of the HLA-A*02 class I molecule and short peptide fragments derived from proteins that are specifically or over-expressed in malignant cells (PMID: 22231555). These complexes are displayed on the surface of cancer cells and serve as the primary recognition signal for the T-cell receptors (TCRs) of cytotoxic CD8+ T lymphocytes, which are essential for the adaptive immune response against tumors (UniProt P01892). In the context of cancer, TAAs such as MAGE-A4, NY-ESO-1, and gp100 are processed and presented by HLA-A*02, allowing the immune system to identify and eliminate cancerous cells (PMID: 38537575). Therapeutic strategies targeting these specific peptide-MHC complexes include TCR-engineered T-cell (TCR-T) therapies, TCR-bispecific engagers (ImmTACs), and peptide-based vaccines (PMID: 34554482). Because these therapies are restricted to the HLA-A*02 allele, patients must undergo HLA typing as a companion diagnostic to ensure eligibility. Significant challenges in targeting these complexes include the risk of off-target toxicity due to TCR cross-reactivity with similar peptides in normal tissues and the potential for tumors to downregulate HLA expression as a mechanism of immune escape (PMID: 23836124).

Other names

HLA-A2-restricted tumor antigenspHLA-A*02 complexesMHC-peptide complexesHLA-A*02:01-presented peptidesHLA-A2-restricted epitopesPeptide-HLA-A*02 complex

T-cell receptor (TCR) binding and T-cell mediated cytotoxicity