HLA-A*02 restricted melanoma-associated antigens (HLA-A2/MAA)

The target group HLA-A*02 restricted melanoma-associated antigens refers to a collection of peptide-major histocompatibility complexes (pMHC) where the Human Leukocyte Antigen A*02 (HLA-A2) allele presents specific immunodominant epitopes derived from melanoma-associated antigens (MAAs) (UniProt P01892). These antigens include lineage-specific proteins like Tyrosinase (UniProt P14679), cancer-testis antigens such as the MAGE family (UniProt P43355) and NY-ESO-1 (CTAG1B, UniProt P12889), and modified enzymes like GnT-V (MGAT5). In malignant melanoma, these peptides are processed and displayed on the cell surface, serving as specific markers for T-cell recognition and immune surveillance (PubMed: 10508511). Therapeutic strategies targeting these complexes, such as T-cell receptor (TCR) engineered T-cells (e.g., Afamitresgene autoleucel) or bispecific T-cell engagers (e.g., Tebentafusp), rely on the high-affinity recognition of the peptide-HLA-A2 complex to direct a potent immune response against the tumor (Nature Reviews Drug Discovery, 2021). Because HLA-A*02:01 is the most prevalent MHC Class I allele in many populations, these complexes are primary targets for personalized immunotherapy in solid tumors. However, successful clinical application requires careful screening for antigen expression and monitoring for potential off-tumor toxicities in tissues that may share these epitopes, such as the skin or eyes.

Other names

HLA-A2-peptide complexesHLA-A*02:01-restricted melanoma antigenspMHC melanoma targetsHLA-A2/NY-ESO-1 complexHLA-A2/MAGE complexHLA-A2/Tyrosinase complex

T-cell receptor (TCR) mediated T-cell redirection and activation against peptide-MHC complexes