Glycoprotein 100 (gp100) peptide presented by Human Leukocyte Antigen A*02:01 (HLA-A*02:01) (gp100/HLA-A*02)

The gp100 peptide presented by HLA-A*02 is a peptide-major histocompatibility complex (pMHC) that serves as a critical target in melanoma immunotherapy [1, 17]. Glycoprotein 100 (gp100), also known as PMEL, is a protein involved in the maturation of melanosomes and is highly expressed in melanocytes and melanoma cells [7, 17]. Specific immunogenic peptides derived from gp100, such as the 280-288 epitope (YLEPGPVTA), are processed and presented on the cell surface by the HLA-A*02:01 allele [1, 17]. This complex is recognized by T-cell receptors (TCRs), making it an ideal target for T-cell redirecting therapies [1, 11]. Tebentafusp (Kimmtrak) is a first-in-class bispecific ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) that binds this pMHC complex with picomolar affinity while simultaneously engaging CD3 on T cells [1, 5]. This interaction facilitates the recruitment and activation of polyclonal T cells, leading to the release of inflammatory cytokines and direct lysis of melanoma cells [3, 14]. Therapeutic use is restricted to patients who are HLA-A*02:01 positive, and common safety concerns include cytokine release syndrome and skin-related toxicities due to the presence of gp100 in normal melanocytes [11, 15].

Other names

gp100-HLA-A*02 complexPMEL-HLA-A*02 complexgp100(280-288)/HLA-A*02:01gp100(209-217)/HLA-A*02:01pMHC complexYLEPGPVTA/HLA-A*02:01

T-cell redirection and activation via bispecific T-cell receptor (TCR) engagement, leading to cytokine release and tumor cell lysis.