Target intelligence / Profile preview

Mouse MHC class I H-2Db human glycoprotein 100 (25-33) peptide complex (H-2Db-hgp100(25-33))

Target
H-2Db-hgp100(25-33)
Molecular classification
MHC class I complex, Antigen-presenting molecule, Peptide-MHC complex
01

Overview

The H-2Db–human gp100:25-33 peptide complex is a molecular assembly consisting of the mouse MHC class I molecule H-2Db and a specific 9-amino acid epitope (KVPRNQDWL) derived from the human glycoprotein 100 (gp100) protein (Overwijk et al., 2003, J. Exp. Med.). This complex is a critical tool in preclinical oncology research, particularly within the pmel-1 mouse model, where it serves as the cognate antigen for T-cell receptors (TCRs) specific to melanoma. In biological systems, the complex is presented on the surface of antigen-presenting cells or tumor cells, where it is recognized by CD8+ T cells, leading to an immune response against melanocytes (Restifo et al., 2012, Nat. Rev. Immunol.). Because gp100 is a lineage-specific antigen overexpressed in melanoma, this complex is a primary target for developing and testing immunotherapies such as peptide vaccines and TCR-engineered T-cell therapies. Therapeutic strategies targeting this complex aim to enhance the body's ability to identify and eliminate melanoma cells, though challenges include potential autoimmune reactions against normal pigmented tissues and tumor-mediated immune evasion.

Other names
H-2Db-gp100(25-33)H-2Db/KVPRNQDWL complexgp100:25-33/H-2DbpMHC complexH-2Db-human gp100:25-33
02

Mechanism of action

The complex acts as a ligand for specific T-cell receptors (TCRs), triggering the activation and proliferation of cytotoxic CD8+ T lymphocytes that target and destroy cells expressing the gp100 antigen (Overwijk et al., 2003, J. Exp. Med.).

03

Biological functions

Antigen presentationT-cell activationImmune responseCD8+ T-cell recognition
04

Disease associations

MelanomaCancer
05

Safety considerations

Autoimmune destruction of healthy melanocytes (vitiligo)Antigen loss or MHC downregulation by tumorsCytokine release syndrome in TCR therapiesOff-target toxicity in pigmented tissues
06

Interacting drugs

gp100:25-33 peptide vaccine

3 more in the full profile.

07

Biomarkers

gp100 expressionH-2Db expressionPmel-1 T-cell frequencyMHC class I surface expression

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