Melanoma-associated peptide–HLA-A*02:01 complex (pHLA-A*02:01) (pHLA-A*02:01)

The Melanoma-associated peptide–HLA-A*02:01 complex is a specialized molecular target on the surface of melanoma cells, formed by the presentation of tumor-derived peptides within the groove of the Human Leukocyte Antigen (HLA) A*02:01 molecule. These peptides typically originate from lineage-specific proteins such as gp100, MART-1, or Tyrosinase, or cancer-testis antigens like MAGE-A4 (D'Angelo et al., 2018, Cancer Discovery). As a member of the MHC Class I family, the complex's primary biological role is to display intracellular proteomic fragments to CD8+ T cells, facilitating the surveillance and destruction of malignant cells. In the context of immunotherapy, this complex is targeted by TCR-engineered T cells and bispecific T-cell engagers like Tebentafusp, which bypasses natural TCR limitations to trigger a potent immune response against uveal and cutaneous melanoma (Nathan et al., 2021, NEJM). The high prevalence of the HLA-A*02:01 allele in many populations makes it a cornerstone for developing TCR-based precision medicines. However, therapeutic efficacy can be limited by the downregulation of HLA molecules by the tumor or by inflammatory side effects resulting from the presence of similar antigens in healthy melanocytes (Gonzalez-Galarza et al., 2020, Nucleic Acids Res).

Other names

Melanoma antigen-MHC class I complexpMHC complexHLA-A2-restricted melanoma antigengp100-HLA-A*02:01 complexMART-1-HLA-A*02:01 complexMAGE-A4-HLA-A*02:01 complex

Therapeutic agents target this complex by utilizing engineered T-cell receptors (TCRs) or bispecific molecules that bind the specific peptide-HLA interface, subsequently recruiting and activating cytotoxic T cells to lyse the tumor cell (Nathan et al., 2021, NEJM).