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Ligand Design for Specific MHC Class I Molecules on the Cell Surface

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journal contribution
posted on 30.11.2020, 14:04 by Xizheng Sun, Reika Tokunaga, Yoko Nagai, Ryo Miyahara, Akihiro Kishimura, Shigeru Kawakami, Yoshiki Katayama, Takeshi Mori
We have validated that ligand peptides designed from antigen peptides could be used for targeting specific major histocompatibility complex class I (MHC-I) molecules on the cell surface. To design the ligand peptides, we used reported antigen peptides for each MHC-I molecule with high binding affinity. From the crystal structure of the peptide/MHC-I complexes, we determined a modifiable residue in the antigen peptides and replaced this residue with a lysine with an ε-amine group modified with functional molecules. The designed ligand peptides successfully bound to cells expressing the corresponding MHC-I molecules via exchange of peptides bound to MHC-I. We demonstrated that the peptide ligands could be used to transport a protein or a liposome to cells expressing the corresponding MHC-I. This strategy may be useful for targeted delivery to cells overexpressing MHC-I, which have been observed in autoimmune diseases.