HLA-A*02:01-MELOE-1 peptide complex (HLA-A2/MELOE-1)

The HLA-A*02:01-MELOE-1 peptide complex is a tumor-specific antigen presentation assembly found on the surface of melanoma cells. It consists of the Human Leukocyte Antigen A*02:01 (HLA-A2) molecule presenting a specific 9-amino acid peptide, TLMSAMTNL, derived from the Melanoma-expressed antigen 1 (MELOE-1) [Godet et al., 2010, PMID: 20143120]. MELOE-1 is a unique tumor-associated antigen encoded by a multi-ORF RNA that is highly overexpressed in melanoma but has very limited expression in normal tissues, except for melanocytes [Bobinet et al., 2012, PMID: 22517957]. This high degree of specificity makes the HLA-A2/MELOE-1 complex an ideal target for T-cell receptor (TCR)-based immunotherapies, such as TCR-engineered T cells and bispecific T-cell engagers like ImmTACs [Immunocore Pipeline, 2024]. These therapeutic agents are designed to recognize the pMHC complex with high affinity, triggering a potent cytotoxic T-lymphocyte response against the tumor cells. Clinical interest in this target is driven by its potential to treat HLA-A2-positive melanoma patients with a reduced risk of systemic toxicity compared to less specific antigens. Monitoring MELOE-1 expression and HLA-A2 status is essential for patient selection in clinical trials targeting this complex.

Other names

HLA-A*02:01/MELOE-1(36-44) complexMELOE-1/HLA-A2 complexMelanoma-expressed antigen 1 peptide-MHC complexTLMSAMTNL-HLA-A*02:01 complex

T-cell redirection and activation via T-cell receptor (TCR) recognition of the peptide-MHC complex, leading to targeted lysis of melanoma cells.