HLA-A*02:01-gp100(280-288) peptide-MHC complex (HLA-A*02:01/gp100(280-288))

The HLA-A*02:01-gp100(280-288) peptide-MHC complex is a specific molecular assembly presented on the surface of cells, primarily melanocytes and melanoma cells (UniProt P17667). It comprises the Human Leukocyte Antigen (HLA) allele A*02:01 and a 9-amino acid peptide (YLEPGPVTA) derived from the gp100 protein, also known as PMEL (PubMed: 10449301). This complex plays a pivotal role in the immune system by acting as a ligand for T-cell receptors (TCRs), allowing CD8+ cytotoxic T cells to identify and eliminate cells expressing the gp100 antigen. In malignant conditions like uveal and cutaneous melanoma, the overexpression of gp100 makes this pMHC complex an ideal target for immunotherapy (NIH: NCT03070392). Therapeutic agents such as tebentafusp (Kimmtrak) are designed to bind specifically to this complex with high affinity (FDA Label: Kimmtrak). By bridging the pMHC on tumor cells with the CD3 receptor on T cells, these drugs trigger a potent immune response against the cancer. The clinical utility of targeting this complex is restricted to patients who are HLA-A*02:01 positive, making the allele a necessary biomarker for treatment.

Other names

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

Tebentafusp is a bispecific protein comprised of a high-affinity T cell receptor (TCR) fused to an anti-CD3 scFv; the TCR domain binds the HLA-A*02:01-gp100(280-288) complex on the tumor cell, while the effector domain binds CD3 on T cells, leading to the formation of an immunological synapse and subsequent tumor cell lysis (FDA Label: Kimmtrak).