HLA-A*02:01-bound gp100 peptide-MHC complex (HLA-A*02:01/gp100 pMHC)

The HLA-A*02:01-bound gp100 peptide-MHC complex is a molecular assembly consisting of the Human Leukocyte Antigen (HLA) allele A*02:01 and a specific peptide epitope derived from the gp100 (PMEL) protein, such as YLEPGPVTA (Nathan et al., 2021, PMID: 34551229). gp100 is a melanocyte-differentiation antigen involved in melanosome biogenesis and is highly overexpressed in melanoma cells, particularly in uveal and cutaneous melanoma (UniProt P40967). This complex is presented on the surface of tumor cells and serves as a critical target for T-cell-based immunotherapies. The most prominent drug targeting this complex is Tebentafusp, a first-in-class bispecific T-cell engager (ImmTAC) that uses a high-affinity T-cell receptor (TCR) domain to bind the pMHC and an anti-CD3 domain to recruit and activate polyclonal T cells. This interaction bypasses the need for natural TCR-MHC affinity, leading to the targeted lysis of gp100-expressing malignant cells. Clinical use of therapies targeting this complex requires patients to be HLA-A*02:01 positive, as the drug's binding is specific to this MHC allele.

Other names

gp100-HLA-A*02:01 complexPMEL-HLA-A*02:01 complexgp100 peptide-MHC complexHLA-A2/gp100gp100(280-288)-HLA-A*02:01 complex

Tebentafusp is a bispecific T-cell engager (ImmTAC) that redirects T cells to kill gp100-expressing cells by binding the pMHC complex via a high-affinity TCR domain and CD3 via an anti-CD3 scFv domain (Nathan et al., 2021, PMID: 34551229).