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

preprint
submitted on 26.08.2020 and posted on 26.08.2020 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 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 the 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. The present strategy may be useful for targeted delivery to cells overexpressing MHC-I, which have been observed autoimmune diseases.

History

Email Address of Submitting Author

mori.takeshi.880@m.kyushu-u.ac.jp

Institution

Kyushu University

Country

Japan

ORCID For Submitting Author

0000-0002-1821-5427

Declaration of Conflict of Interest

The authors have declared no conflict of interest.

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