Target intelligence / Profile preview

Tyrosinase-related protein 2-derived HLA-A*0201-restricted epitope (TRP-2/HLA-A*0201)

Target
TRP-2/HLA-A*0201
Molecular classification
Antigen, Peptide, MHC-peptide complex
01

Overview

The Tyrosinase-related protein 2 (TRP-2)-derived HLA-A*0201-restricted epitope is a specific antigenic peptide, most notably the nonamer SVYDFFVWL (residues 180-188), that is presented by the Human Leukocyte Antigen (HLA) A*0201 molecule (Parkhurst et al., 1998, J Immunol). TRP-2, also known as dopachrome tautomerase (DCT), is an enzyme in the melanosomal pathway that is highly expressed in melanocytes and overexpressed in melanoma and glioblastoma multiforme (Wang et al., 1996, J Exp Med). This epitope is a primary target for cancer immunotherapies, including peptide-based vaccines like ICT-107 and TCR-engineered T-cell therapies, which aim to prime the immune system to recognize and destroy malignant cells (Phuphanich et al., 2013, Cancer Immunol Immunother). By binding to the HLA-A*0201 complex, the peptide facilitates the activation of CD8+ cytotoxic T lymphocytes, leading to targeted tumor cell lysis. However, because TRP-2 is also expressed in normal melanocytes, a significant safety concern is the development of vitiligo, an autoimmune condition characterized by skin depigmentation. Monitoring HLA-A*0201 status and TRP-2 expression levels is essential for patient selection and evaluating therapeutic efficacy.

Other names
TRP-2(180-188)SVYDFFVWLDopachrome tautomerase-derived HLA-A2 epitopeTRP2-A2DCT-derived epitope
02

Mechanism of action

Induction of cytotoxic T lymphocyte (CTL) responses against tumor cells expressing TRP-2 through MHC class I presentation.

03

Biological functions

Immune responseAntigen presentationT-cell activation
04

Disease associations

MelanomaGlioblastomaCancer
05

Safety considerations

VitiligoAutoimmune response against normal melanocytesTherapeutic resistance via HLA downregulation
06

Interacting drugs

ICT-107

3 more in the full profile.

07

Biomarkers

HLA-A*0201 genotypeTRP-2 protein expressionTRP-2-specific CD8+ T-cell count

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