Human leukocyte antigen A*02:01–glycoprotein 100 peptide complex (HLA-A*02:01–gp100)

The HLA-A*02:01–gp100 peptide complex is a specific molecular assembly consisting of the Human Leukocyte Antigen (MHC Class I) allele A*02:01 and a processed peptide fragment derived from the gp100 (PMEL) protein (UniProt P40967). This complex is primarily expressed on the surface of melanocytes and melanoma cells, as well as on professional antigen-presenting cells like dendritic cells during immune priming (PubMed: 10426712). In the context of oncology, it serves as a critical target for immunotherapy because gp100 is highly overexpressed in melanoma compared to most normal tissues (PubMed: 21632438). Therapeutic strategies targeting this complex include bispecific T-cell engagers, such as Tebentafusp, which bridge the MHC-peptide complex with T-cell receptors to induce tumor cell lysis (FDA Label: Kimmtrak). Additionally, peptide vaccines and TCR-engineered T-cell therapies are designed to specifically recognize this complex to enhance the anti-tumor immune response (PubMed: 11342590). While effective, targeting this complex can lead to autoimmune-like side effects, such as vitiligo, due to the presence of gp100 in normal melanocytes. The specificity of the HLA-A*02:01 allele restricts these therapies to patients carrying this particular genetic marker, which is found in approximately 50% of Caucasians (Allele Frequency Net Database).

Other names

HLA-A2/gp100 complexMHC-peptide complex (gp100)PMEL-derived peptide-HLA-A*02:01 complexgp100:209-217(210M)-HLA-A2 complexHLA-A*02:01/PMEL complex

T-cell redirection via bispecific TCR-anti-CD3 fusion protein and TCR-mediated recognition of MHC-presented peptides (FDA Label: Kimmtrak).