HLA-A*02:01-presented glycoprotein 100 (209-217) peptide complex (HLA-A*02:01/gp100(209-217))

The HLA-A*02:01-presented glycoprotein 100 (209-217) peptide complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a therapeutic target in melanoma. Gp100 (also known as PMEL) is a melanocyte-lineage protein involved in the formation of melanosomes, and its 209-217 epitope (ITDQVPFSV) is processed and presented on the cell surface by the HLA-A*02:01 allele (UniProt: P40967, P01892). This complex is highly expressed in both cutaneous and uveal melanoma cells, making it an ideal target for T-cell receptor (TCR)-based therapies. Tebentafusp, the first-in-class ImmTAC (Immune mobilizing monoclonal TCR Against Cancer), specifically recognizes this pMHC complex to redirect T-cells to kill tumor cells (Nathan et al., NEJM 2021). The interaction involves a high-affinity TCR domain binding the pMHC and an anti-CD3 effector domain engaging T-cells. Because gp100 is also expressed in healthy melanocytes, treatment often results in manageable skin-related side effects like rash or vitiligo. Clinical efficacy is strictly dependent on the patient's HLA-A*02:01 status, necessitating companion diagnostic testing. This target represents a significant advancement in treating HLA-restricted cancers using soluble TCR technology.

Other names

gp100:209-217-HLA-A*02:01PMEL-derived peptide-MHC complexg209-2M peptide-HLA complexHLA-A2/gp100

Redirection of T-cells to target cells via a bispecific T-cell receptor (TCR) fusion protein that binds the pMHC complex and CD3.