Human leukocyte antigen A2 presenting glycoprotein 100 epitopes (HLA-A2/gp100)

The HLA-A2 presenting gp100 epitopes target is a peptide-major histocompatibility complex (pMHC) found on the surface of melanocytes and melanoma cells (Nathan et al., 2021). It consists of the HLA-A*02:01 molecule presenting specific immunogenic peptides derived from the glycoprotein 100 (gp100/PMEL) protein, a lineage-specific antigen involved in melanosome biogenesis (Damato et al., 2019). This complex serves as a critical recognition site for the immune system, specifically for T-cell receptors (TCRs) that monitor for overexpressed self-antigens in malignancies (Middleton et al., 2020). In the context of oncology, this target is highly relevant for uveal and cutaneous melanoma, where gp100 is frequently overexpressed (Hassel et al., 2023). Therapeutic strategies, such as the bispecific fusion protein tebentafusp, utilize a high-affinity TCR domain to bind this pMHC complex while simultaneously engaging CD3 on T-cells (FDA, 2022). This redirection of T-cells leads to the targeted lysis of melanoma cells regardless of natural TCR specificity, provided the patient carries the HLA-A*02:01 allele (Nathan et al., 2021).

Other names

HLA-A*02:01/gp100 complexPMEL-HLA-A2 complexgp100-HLA-A2 pMHCMHC-gp100 complexHLA-A2-PMEL complex

T-cell redirection via bispecific TCR-CD3 engagement targeting the peptide-MHC complex