Major histocompatibility complex class I and II presentation of melanoma-associated antigens (MHC-I/II MAA presentation)

MHC class I and II presentation of melanoma-associated antigens (MAAs) is the biological process by which melanoma cells process internal proteins into short peptides and display them on the cell surface via Major Histocompatibility Complex (MHC) molecules (Garrido et al., 2016, PMID: 26903100). MHC class I molecules typically present these peptides to CD8+ cytotoxic T cells, while MHC class II molecules present them to CD4+ helper T cells, facilitating a coordinated anti-tumor immune response (Rock et al., 2016, PMID: 26703101). Key antigens involved include lineage-specific proteins like gp100 (PMEL), MART-1 (MLANA), and tyrosinase, as well as cancer-testis antigens like MAGE-A3 and NY-ESO-1 (Boon et al., 2006, PMID: 16446354). This presentation mechanism is the foundation for several classes of immunotherapy, including TCR-engineered T-cell therapies and bispecific T-cell engagers like tebentafusp, which specifically recognize the peptide-MHC complex (Nathan et al., 2021, PMID: 34551229). However, melanoma cells often employ immune escape strategies such as the downregulation of MHC molecules or mutations in Beta-2 Microglobulin (B2M) to avoid T-cell recognition (Zaretsky et al., 2016, PMID: 27411683). Consequently, maintaining or restoring effective antigen presentation is a major focus of current oncological research and drug development.

Other names

Antigen processing and presentation of melanoma antigensHLA presentation of melanoma-associated antigensMHC-restricted melanoma antigen presentationMelanoma antigen presentation pathway

Recognition of specific peptide-MHC complexes by engineered T-cell receptors or bispecific engagers, and enhancement of antigen presentation through vaccines or cytokine-mediated upregulation of MHC expression.