Human leukocyte antigen (HLA) class I and II molecules presenting MART-1, gp100, and tyrosinase epitopes (HLA-MAA complexes)

Human leukocyte antigen (HLA) class I and II molecules presenting epitopes from MART-1 (Melan-A), gp100 (PMEL), and tyrosinase are primary targets for melanoma immunotherapy. These proteins are melanocyte differentiation antigens (MDAs) that are highly expressed in both normal melanocytes and melanoma cells (Kawakami et al., 1994; Bakker et al., 1994). When these proteins are processed into peptides and presented by HLA molecules, they form peptide-MHC (pMHC) complexes that can be recognized by the T-cell receptors (TCRs) of cytotoxic and helper T cells (Brichard et al., 1993). Therapeutic interventions such as Tebentafusp, TCR-engineered T cells, and peptide vaccines are designed to exploit these complexes to induce a targeted anti-tumor immune response (Nathan et al., 2021). Because these antigens are also present in healthy tissues like the skin, eye, and inner ear, treatments targeting them can lead to on-target, off-tumor toxicities such as vitiligo and uveitis. Despite these challenges, these HLA-presented epitopes remain cornerstone targets in the development of precision immunotherapies for metastatic melanoma.

Other names

Melanocyte differentiation antigen-HLA complexesMelanoma-associated antigen (MAA) peptide-MHC complexesHLA-restricted MART-1/gp100/Tyrosinase epitopesMelanoma differentiation antigen-HLA complexes

T-cell receptor (TCR) mediated recognition of specific peptide-HLA complexes leading to T-cell activation and subsequent lysis of tumor cells.