Identification of peptide mimetics of xenoreactive alpha-Gal antigenic epitope by phage display

Biochemical and Biophysical Research Communications
Jianshe LangZhikun Yan

Abstract

The prevention of hyperacute rejection (HAR) triggered by interaction between the human natural antibody and xenoreactive antigenic epitope (Gal-alpha1, 3Gal) present on pig cells is the key to success in pig-to-human xenotransplantation. The phage display technology offers an effective strategy for screening peptides which can interact with the anti-Gal antibody to block alpha-Gal antigen binding site. Two peptide libraries, linear 7 peptide library and C7C library, were panned on the anti-B monoclonal antibody which has the characteristic of binding to the alpha-Gal antigenic epitope. After four rounds of panning, 22 positive phage clones were selected. Highly homologous sequence PT and STL existed among these selected peptides. Stachyose competitive ELISAs revealed that these peptides specifically bound to alpha-Gal antigen binding site. Eight peptide mimics of alpha-Gal antigenic epitope could inhibit the agglutination of pig red blood cells mediated by human sera in a dose-dependent manner. These results demonstrated that the selected peptides can mimic the conformational structure of alpha-Gal antigenic epitope and have the therapeutic potential in xenotransplantation.

References

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Citations

May 16, 2008·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Zhaoming TangLifang Dou
Feb 28, 2007·Clinical and Experimental Pharmacology & Physiology·Tamaki TakagiMakoto Sawada
Mar 17, 2009·BMC Research Notes·Laura L Eggink, J Kenneth Hoober
May 31, 2014·PLoS Neglected Tropical Diseases·Nágilla Daliane FelicianoJulia Maria Costa-Cruz
Jan 12, 2011·Expert Opinion on Biological Therapy·Mark AgostinoElizabeth Yuriev
Jan 21, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Fahriye Ceyda DudakBrendan P Orner
Aug 24, 2006·Xenotransplantation·Reto M Baertschiger, Leo H Buhler
Feb 9, 2021·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Léo BoussametLaureline Berthelot

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