Major Histocompatibility Complex class I-gp100 peptide complex (MHC I-gp100)

The Major Histocompatibility Complex (MHC) class I-gp100 peptide complex is a specialized molecular target formed by the presentation of peptides derived from the melanocyte-specific protein PMEL (gp100) on the surface of cells via MHC class I molecules, predominantly HLA-A*02:01 (UniProt: P40967). gp100 is a transmembrane glycoprotein essential for the maturation of melanosomes and is highly expressed in both normal melanocytes and melanoma cells (PubMed: 34551229). In the context of oncology, this complex serves as a tumor-associated antigen that can be recognized by the T-cell receptor (TCR) of cytotoxic T lymphocytes. Therapeutic interventions, such as the bispecific T-cell engager Tebentafusp, are designed to bind specifically to this peptide-MHC complex with high affinity while simultaneously engaging the CD3 receptor on T cells (PubMed: 35236848). This redirection of T cells leads to the targeted lysis of melanoma cells, particularly in uveal melanoma where gp100 is consistently expressed. However, because gp100 is also present in healthy melanocytes, treatment can result in on-target, off-tumor toxicities affecting the skin and eyes. Additionally, the therapy is restricted to patients who carry the specific HLA-A*02:01 allele, necessitating companion diagnostic testing.

Other names

HLA-A*02:01-gp100 complexPMEL-MHC complexgp100-HLA-A2 complexMelanocyte protein PMEL peptide-MHC

T-cell redirection via bispecific T-cell receptor (TCR) fusion proteins that bind the peptide-MHC complex and CD3