HLA-A*02:01-gp100(280-288) peptide complex (HLA-A2/gp100(280-288))

The HLA-A*02:01-gp100(280-288) peptide complex is a specific antigen-presenting structure found on the surface of melanoma cells and normal melanocytes. It consists of the Major Histocompatibility Complex (MHC) Class I allele HLA-A*02:01 presenting a 9-amino acid epitope (YLEPGPVTA) derived from the gp100 (PMEL) protein (Nathan et al., 2021, NEJM). This complex is a validated therapeutic target, particularly in uveal and cutaneous melanoma, where gp100 is frequently overexpressed (Damato et al., 2023, Cancers). The primary therapeutic approach involves the use of T-cell receptor (TCR) based molecules, such as tebentafusp, which is a bispecific fusion protein (ImmTAC) designed to bind this pMHC complex with high affinity while simultaneously engaging CD3 on T cells (Middleton et al., 2020, Clinical Cancer Research). This interaction bypasses natural TCR limitations to induce a potent immune response against tumor cells. Because the target includes a specific HLA allele, treatment is restricted to patients who are HLA-A*02:01 positive, making the HLA genotype a critical biomarker for patient selection (FDA, 2022, Kimmtrak Prescribing Information). Safety concerns primarily involve cytokine release syndrome and skin-related toxicities due to the presence of gp100 in healthy melanocytes (Hassel et al., 2023, Nature Medicine). This target represents a significant advancement in TCR-based immunotherapy, providing a bridge between the specificity of the adaptive immune system and the potency of redirected T-cell cytotoxicity.

Other names

HLA-A*02:01-YLEPGPVTA complexgp100:280-288/HLA-A2 complexPMEL:280-288/HLA-A*02:01gp100(280-288) peptide-MHC complex

Bispecific T-cell engager (ImmTAC) binding to the pMHC complex and CD3 to redirect T-cell cytotoxicity.