HLA-A*02:01-tyrosinase (368-376, 370D) peptide complex (HLA-A*02:01/Tyr368-376(370D))

The HLA-A*02:01-tyrosinase (368-376, 370D) peptide complex is a specific antigen-presenting structure found on the surface of melanoma cells and normal melanocytes. It consists of the Human Leukocyte Antigen (HLA) allele A*02:01 presenting a fragment of the tyrosinase enzyme, which is essential for melanin production. The specific peptide sequence (residues 368-376) typically undergoes a post-translational deamidation where asparagine at position 370 is converted to aspartic acid (370D), a modification that significantly increases its binding stability to the HLA molecule and its recognition by T-cell receptors (TCRs) (Skipper et al., 1996, J Exp Med). This complex is a primary target for advanced immunotherapies, including TCR-engineered T-cell (TCR-T) therapies, such as Medigene's MDG1021, and various peptide vaccines aimed at treating metastatic melanoma (Wolfel et al., 1994, Eur J Immunol). Because tyrosinase expression is shared with healthy pigment-producing cells, therapeutic targeting of this complex can lead to on-target, off-tumor toxicities such as vitiligo or ocular inflammation. Clinical development focuses on optimizing TCR affinity to maximize anti-tumor efficacy while managing these autoimmune-like side effects.

Other names

HLA-A*02:01-YMDGTMSQV complexTyrosinase 368-376 (370D) peptide-MHC complexHLA-A2-restricted tyrosinase 370D antigenDeamidated tyrosinase(368-376) HLA-A2 complex

Recognition of the peptide-MHC complex by engineered or endogenous T-cell receptors (TCRs) triggers the activation of cytotoxic T-lymphocytes, leading to the targeted lysis of tyrosinase-expressing tumor cells through the release of perforins and granzymes.