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

被引:22
作者
Lang, HS [1 ]
Zhan, JB [1 ]
Xu, LH [1 ]
Yan, ZK [1 ]
机构
[1] Zhejiang Univ, Dept Biochem, Sch Med, Hangzhou 310006, Peoples R China
基金
中国国家自然科学基金;
关键词
peptide mimics; xenoreactive antigen; xenotransplantation; phage display;
D O I
10.1016/j.bbrc.2006.03.112
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The prevention of hyperacute rejection (HAR) triggered by interaction between the human natural antibody and xenoreactive antigenic epitope (Gal-alpha 1,3Gal) 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. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:214 / 220
页数:7
相关论文
共 21 条
[1]   EPITOPE DISCOVERY USING PEPTIDE LIBRARIES DISPLAYED ON PHAGE [J].
CORTESE, R ;
FELICI, F ;
GALFRE, G ;
LUZZAGO, A ;
MONACI, P ;
NICOSIA, A .
TRENDS IN BIOTECHNOLOGY, 1994, 12 (07) :262-267
[2]   A GENERAL STRATEGY TO IDENTIFY MIMOTOPES OF PATHOLOGICAL ANTIGENS USING ONLY RANDOM PEPTIDE LIBRARIES AND HUMAN SERA [J].
FOLGORI, A ;
TAFI, R ;
MEOLA, A ;
FELICI, F ;
GALFRE, G ;
CORTESE, R ;
MONACI, P ;
NICOSIA, A .
EMBO JOURNAL, 1994, 13 (09) :2236-2243
[3]   Significance of anti-Gal IgG in chronic xenograft rejection [J].
Galili, U .
TRANSPLANTATION PROCEEDINGS, 1999, 31 (1-2) :940-941
[4]   INTERACTION OF THE NATURAL ANTI-GAL ANTIBODY WITH ALPHA-GALACTOSYL EPITOPES - A MAJOR OBSTACLE FOR XENOTRANSPLANTATION IN HUMANS [J].
GALILI, U .
IMMUNOLOGY TODAY, 1993, 14 (10) :480-482
[5]   The α-gal epitope (Galα1-3Galβ1-4GlcNAc-R) in xenotransplantation [J].
Galili, U .
BIOCHIMIE, 2001, 83 (07) :557-563
[6]   APPLICATIONS OF COMBINATORIAL TECHNOLOGIES TO DRUG DISCOVERY .1. BACKGROUND AND PEPTIDE COMBINATORIAL LIBRARIES [J].
GALLOP, MA ;
BARRETT, RW ;
DOWER, WJ ;
FODOR, SPA ;
GORDON, EM .
JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (09) :1233-1251
[7]   PEPTIDE LIGANDS FOR INTEGRIN ALPHA(V)BETA(3) SELECTED FROM RANDOM PHAGE DISPLAY LIBRARIES [J].
HEALY, JM ;
MURAYAMA, O ;
MAEDA, T ;
YOSHINO, K ;
SEKIGUCHI, K ;
KIKUCHI, M .
BIOCHEMISTRY, 1995, 34 (12) :3948-3955
[8]   IDENTIFICATION OF HIV VACCINE CANDIDATE PEPTIDES BY SCREENING RANDOM PHAGE EPITOPE LIBRARIES [J].
KELLER, PM ;
ARNOLD, BA ;
SHAW, AR ;
TOLMAN, RL ;
VANMIDDLESWORTH, F ;
BONDY, S ;
RUSIECKI, VK ;
KOENIG, S ;
ZOLLAPAZNER, S ;
CONARD, P ;
EMINI, EA ;
CONLEY, AJ .
VIROLOGY, 1993, 193 (02) :709-716
[9]   Identification and characterization of a galactosyl peptide mimetic - Implications for use in removing xenoreactive anti-A Gal antibodies [J].
Kooyman, DL ;
McClellan, SB ;
Parker, W ;
Avissar, PL ;
Velardo, MA ;
Platt, JL ;
Logan, JS .
TRANSPLANTATION, 1996, 61 (06) :851-855
[10]   Molecular barriers to xenotransplantation [J].
Lawson, JH ;
Platt, JL .
TRANSPLANTATION, 1996, 62 (03) :303-310