HLA class I antigen, A-1 alpha chain (HLA-A1) (HLA-A1)

HLA-A1 (Human Leukocyte Antigen A1) is a specific serotype of the HLA-A locus, belonging to the Major Histocompatibility Complex (MHC) class I family (UniProt P30443; NCBI Gene ID: 3105). Its primary biological role is the presentation of endogenous peptides, derived from both self-proteins and foreign or mutated proteins, to the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (UniProt P30443). In oncology, HLA-A1 is a critical restriction element for the recognition of tumor-associated antigens, such as MAGE-A3, making it a focal point for the development of TCR-engineered T-cell (TCR-T) therapies and cancer vaccines (PMID: 23585431; ClinicalTrials.gov NCT01352234). These therapies rely on the precise binding of a TCR to the HLA-A1/peptide complex to trigger a targeted immune attack against malignant cells (ClinicalTrials.gov NCT01352234). However, a significant challenge in targeting HLA-A1-restricted antigens is the risk of off-target toxicity, as demonstrated by historical clinical trials where TCRs cross-reacted with similar peptides in healthy tissues like the heart (PMID: 23585431). Furthermore, tumors often employ immune evasion strategies such as the downregulation or loss of HLA-A1 expression to avoid T-cell detection (NCBI Gene ID: 3105). Understanding the specific peptide-binding motifs of HLA-A1 is essential for patient stratification and the design of safe, effective immunotherapies (PMID: 23585431; PMID: 23479570).

Other names

HLA-A*01MHC class I antigen A*01HLA-A*01:01Human leukocyte antigen A1MHC class I antigen A-1 alpha chain

HLA-A1 functions by binding intracellularly processed peptide fragments and presenting them on the cell surface for recognition by CD8+ T-cell receptors, thereby initiating a cytotoxic immune response against infected or malignant cells (UniProt P30443; NCBI Gene ID: 3105).