Glycoprotein 100-derived peptide–Human Leukocyte Antigen-A*02:01 complex (gp100–HLA-A*02:01)

The gp100-derived peptide–HLA-A*02:01 complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for cancer immunotherapy, particularly in melanoma (Source: aacrjournals.org, nih.gov). It consists of a peptide fragment derived from the glycoprotein 100 (gp100/PMEL) protein, which is presented on the cell surface by the HLA-A*02:01 allele of the MHC Class I molecule (Source: nih.gov, biocytogen.com). This complex is highly expressed on melanoma cells, including those in uveal and cutaneous melanoma, but is also present on normal melanocytes in the skin and eye (Source: nih.gov, drugdevletter.com). Therapeutic strategies targeting this complex include bispecific T-cell engagers like tebentafusp, which utilize an affinity-enhanced T-cell receptor (TCR) to bind the pMHC and an anti-CD3 domain to recruit cytotoxic T cells (Source: aacrjournals.org, drugdevletter.com). Additionally, peptide vaccines have been developed to stimulate an endogenous immune response against this specific epitope (Source: rcsb.org, caregate.net). Clinical use of these therapies requires patients to be HLA-A*02:01 positive, as the drug's binding is highly specific to this allele (Source: drugdevletter.com). Common side effects associated with targeting this complex include skin-related toxicities, such as rash and vitiligo, and systemic cytokine release syndrome (Source: drugdevletter.com, nih.gov). Monitoring for gp100 expression and HLA-A*02:01 status is essential for patient selection and treatment efficacy (Source: drugdevletter.com).

Other names

gp100–HLA-A2 complexPMEL–HLA-A*02:01 complexgp100(209-217)–HLA-A*02:01 complexgp100 peptide–MHC complexSILV–HLA-A*02:01 complex

Tebentafusp is a bispecific T-cell engager that binds the gp100–HLA-A*02:01 complex on tumor cells and CD3 on T cells, leading to T-cell activation and tumor cell lysis. Peptide vaccines aim to induce an endogenous cytotoxic T-lymphocyte response against cells presenting the gp100 epitope.