Major Histocompatibility Complex molecules presenting 763SIP8 peptides to T cell receptors (MHC-763SIP8)

The Major Histocompatibility Complex (MHC) molecules presenting 763SIP8 peptides represent a specific antigen-presenting complex targeted in immunotherapy. The 763SIP8 peptide is a specific epitope derived from the gp100 (glycoprotein 100) protein, which is frequently overexpressed in melanoma and other solid tumors. This peptide is typically presented by the HLA-A*02:01 allele, forming a unique molecular surface that can be recognized by T cell receptors (TCRs). In a therapeutic context, this complex is targeted by bispecific molecules such as Tebentafusp, which utilize a high-affinity TCR domain to bind the pMHC and an anti-CD3 domain to activate polyclonal T cells against the tumor. This interaction bypasses the need for natural TCR recognition, effectively redirecting the immune system to eliminate cells displaying the 763SIP8 epitope. The specificity of this target is crucial for minimizing off-target effects, although safety concerns like cytokine release syndrome remain a challenge in clinical application.

Other names

HLA-A*02:01-763SIP8 complexMHC-peptide complex (763SIP8)pMHC (763SIP8)

Bispecific T cell engager (ImmTAC) that binds the MHC-peptide complex via a high-affinity TCR domain and recruits T cells via an anti-CD3 domain.