Human leukocyte antigen A*02:01-tumor-associated antigen peptide complex (HLA-A2-TAA complex)

The Human leukocyte antigen A*02:01-tumor-associated antigen peptide complex (HLA-A2-TAA) is a molecular assembly consisting of the MHC class I molecule HLA-A*02:01 and a short peptide fragment derived from proteins within a tumor cell [1]. This complex is displayed on the surface of cancer cells, serving as a molecular barcode that signals the presence of abnormal or overexpressed proteins to the immune system [2]. Recognition of these complexes by specific T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes is a fundamental step in the natural anti-tumor immune response [3]. In modern oncology, this complex is a primary therapeutic target for TCR-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers, such as Tebentafusp, which redirect the immune system to kill cells presenting these specific markers [4]. Because HLA-A*02:01 is highly prevalent in many populations, it is the most common MHC allele used for developing peptide-specific immunotherapies [1]. However, the success of targeting these complexes depends on the high specificity of the TCR for the peptide to avoid cross-reactivity with similar peptides in healthy tissues [3]. Additionally, tumors may develop resistance by downregulating HLA expression or through the loss of the specific antigen [1].

Other names

HLA-A*02:01-peptide complexpMHC complexMHC-I-peptide complexHLA-A2-neoantigen complexPeptide-MHC class I complex

T-cell receptor (TCR) mediated recognition of peptide-MHC complexes leading to T-cell activation and tumor cell lysis.