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

The Human leukocyte antigen A*02:01 (HLA-A*02:01) complex presenting peptides from MART-1, gp100, and tyrosinase is a primary target for T-cell based immunotherapies in melanoma. HLA-A*02:01 is a Major Histocompatibility Complex (MHC) Class I molecule that presents endogenously processed peptides to the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (PMID: 15083864). MART-1, gp100, and tyrosinase are lineage-specific differentiation antigens that are overexpressed in the majority of melanomas, making their peptide-MHC complexes ideal targets for immune recognition (PMID: 10449301). Drugs such as Tebentafusp, a bispecific TCR-anti-CD3 fusion protein, specifically target the gp100 peptide presented by HLA-A*02:01 to redirect T cells to tumor cells (PMID: 34551229). Other therapeutic approaches include the use of TCR-engineered T-cells (TCR-T) and peptide vaccines designed to expand the population of T cells specific to these complexes (PMID: 19147751). While effective, these therapies face challenges such as on-target off-tumor toxicity, where T cells attack normal melanocytes in the skin, eyes, and ears, leading to conditions like vitiligo or uveitis (PMID: 21810919). Additionally, tumor escape through HLA downregulation or antigen loss remains a significant hurdle in clinical efficacy.

Other names

HLA-A2/MART-1 complexHLA-A2/gp100 complexHLA-A2/tyrosinase complexMelanoma-associated antigen peptide-MHC complexesHLA-A*02:01/MLANAHLA-A*02:01/PMELHLA-A*02:01/TYR

T-cell receptor (TCR) mediated recognition of peptide-MHC complexes leading to CD8+ T-cell activation and cytotoxic lysis of target cells.