Human leukocyte antigen A*02:01 presenting tyrosinase, gp100, and MART-1 peptides (HLA-A*02:01/MAA complex)

The Human leukocyte antigen A*02:01 (HLA-A*02:01) presenting tyrosinase, gp100, and MART-1 peptides complex is a primary target for T-cell-based immunotherapy in malignant melanoma. HLA-A*02:01 is the most prevalent MHC Class I allele in Caucasian populations and serves to present intracellular peptide fragments to CD8+ cytotoxic T lymphocytes (CTLs) [PMID: 11007341]. Tyrosinase, gp100 (also known as PMEL), and MART-1 (Melan-A) are melanoma differentiation antigens (MDAs) that are highly expressed in both normal melanocytes and melanoma cells [PMID: 8107777]. The presentation of these specific peptides within the HLA-A*02:01 groove allows the immune system to distinguish and target cells of melanocytic origin. Therapeutic interventions such as tebentafusp, a bispecific T-cell engager, specifically target the gp100 peptide/HLA-A*02:01 complex to redirect T cells against tumor cells [PMID: 34551227]. Other modalities include T-cell receptor (TCR) engineered T-cell therapies and peptide-based vaccines designed to elicit a robust CTL response against these antigens [PMID: 19633199]. Because these targets are also present on healthy melanocytes, clinical challenges include on-target off-tumor toxicities such as vitiligo, uveitis, and hearing loss, alongside systemic risks like cytokine release syndrome.

Other names

HLA-A2-restricted melanoma-associated antigenspMHC complexHLA-A*02:01/gp100/MART-1/TyrosinaseMelanoma differentiation antigen/HLA-A2 complex

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, leading to T-cell activation, redirection, and cytotoxic lysis of the target cell.