首页 | 本学科首页   官方微博 | 高级检索  
     


Immunogenicity of a non-repetitive sequence of Plasmodium falciparum circumsporozoite protein in man and mice
Authors:G. Del Giudice   Q. Cheng   D. Mazier   N. Berbiguier   J. A. Cooper   H. D. Engers   C. Chizzolini   A. S. Verdini   F. Bonelli   A. Pessi     P.-H. Lambert
Affiliation:Department of Pathology, University of Geneva, Switzerland.
Abstract:In the present work, the hypothesis that individuals naturally exposed to Plasmodium falciparum malaria infection in endemic areas produce antibodies directed against non-repetitive epitopes of the circumsporozoite protein was investigated. Using a synthetic peptide reproducing the non-repetitive group-conserved region I sequence, we have shown that specific anti-region I antibodies are detectable in sera from endemic countries. Of these sera, 87% also had antibodies against the immunodominant repetitive epitope (Asn-Ala-Asn-Pro, NANP) of P. falciparum. In order to study the immunogenicity of this non-repetitive epitope, a synthetic peptide consisting of both region I and three (NANP) repeats [RI-(NANP)3] was used to immunize inbred strains of mice. H-2b mice produced antibodies against both the repetitive and the non-repetitive epitope. These antibodies were specific for each epitope, recognized P. falciparum sporozoites in immunofluorescence, and inhibited sporozoite penetration into human liver cells in vitro. Non-H-2b mice were completely unresponsive. Lymph node cells from H-2b mice immunized with RI-(NANP)3 peptide proliferated in the presence of RI-(NANP)3 and of (NANP)4 peptide, but never in the presence of RI peptide alone. These findings demonstrate that in the configuration used (i) the non-repetitive epitope region I does not carry T-helper epitopes; (ii) the (NANP) repetitive epitope may act as a carrier for the immune response to region I in mice; and (iii) therefore, immune response to region I in man probably depends on the recognition of T-cell epitopes similar to those involved in the anti-NANP response: i.e. such a T epitope may be NANP itself in responding individuals or another, not yet recognized, sporozoite T-cell epitope.
Keywords:
正在获取引用信息，请稍候...
相似文献(共20条):
[1]、Alloueche A,Silveira H,Conway DJ,Bojang K,Doherty T,Cohen J,Pinder M,Greenwood BM.High-throughput sequence typing of T-cell epitope polymorphisms in Plasmodium falciparum circumsporozoite protein[J].Molecular and biochemical parasitology,2000,106(2):273-282.
[2]、Didier Grillot,Antonello Pessi,Antonio S. Verdini,Paul-Henri Lambert,Giuseppe Del Giudice.Reduced antibody response to the repetitive sequence of the Plasmodium falciparum circumsporozoite protein in mice infected with Plasmodium yoelii blood forms[J].Medical microbiology and immunology,1990,179(5):237-244.
[3]、M J Lockyer.Clonal variation in the Plasmodium falciparum circumsporozoite protein gene[J].Molecular and biochemical parasitology,1991,45(1):179-181.
[4]、Rathore D,McCutchan TF.Heparin can regulate the binding of Plasmodium falciparum circumsporozoite protein[J].Molecular and biochemical parasitology,2000,108(2):253-256.
[5]、T F McCutchan,A A Lal,V do Rosario,A P Waters.Two types of sequence polymorphism in the circumsporozoite gene of Plasmodium falciparum.[J].Molecular and biochemical parasitology,1992,50(1):37-45.
[6]、J L Weber,W T Hockmeyer.Structure of the circumsporozoite protein gene in 18 strains of Plasmodium falciparum[J].Molecular and biochemical parasitology,1985,15(3):305-316.
[7]、D Stüber,W Bannwarth,J R Pink,R H Meloen,H Matile.New B cell epitopes in the Plasmodium falciparum malaria circumsporozoite protein.[J].European journal of immunology,1990,20(4):819-824.
[8]、Jesuíno BS,Casimiro C,do Rosário VE,Silveira H.Effect of antibodies on the expression of Plasmodium falciparum circumsporozoite protein gene[J].International journal of medical sciences,2006,3(1):7-10.
[9]、Kolodny N,Kitov S,Vassell MA,Miller VL,Ware LA,Fegeding K,De La Vega P,Sacci JB,Lanar DE.Two-step chromatographic purification of recombinant Plasmodium falciparum circumsporozoite protein from Escherichia coli[J].Journal of chromatography. B, Biomedical sciences and applications,2001,762(1):77-86.
[10]、V Udhayakumar, Y P Shi, S Kumar, D L Jue, R M Wohlhueter, and,A A Lal.Antigenic diversity in the circumsporozoite protein of Plasmodium falciparum abrogates cytotoxic-T-cell recognition.[J].Infection and immunity,1994,62(4):1410-1413.
[11]、D Rathore,S Kumar,D E Lanar,T F McCutchan.Disruption of disulfide linkages of the Plasmodium falciparum circumsporozoite protein: effects on cytotoxic and antibody responses in mice.[J].Molecular and biochemical parasitology,2001,118(1):75-82.
[12]、S L Hoffman,R Wistar,W R Ballou,M R Hollingdale,R A Wirtz,I Schneider,H A Marwoto,W T Hockmeyer.Immunity to malaria and naturally acquired antibodies to the circumsporozoite protein of Plasmodium falciparum[J].The New England journal of medicine,1986,315(10):601-606.
[13]、黄建生,张丽芸,郭明秋.恶性疟复合多价抗原基因在小鼠中免疫应答的初步研究[J].中华微生物学和免疫学杂志,1998,18(6):457-1.
[14]、A. E. Brown,,D. Chandanayingyong,,S. V. Fuggle, H. K. Webster.Immune responses to the circumsporozoite protein of Plasmodium falciparum in relation to HLA-DR type[J].Tissue antigens,1989,34(3):200-204.
[15]、Kumar A,Kumar S,Le TP,Southwood S,Sidney J,Cohen J,Sette A,Hoffman SL.HLA-A*01-restricted cytotoxic T-lymphocyte epitope from the Plasmodium falciparum circumsporozoite protein[J].Infection and immunity,2001,69(4):2766-2771.
[16]、M Theisen, G Cox, B Hgh, S Jepsen, and,J Vuust.Immunogenicity of the Plasmodium falciparum glutamate-rich protein expressed by vaccinia virus.[J].Infection and immunity,1994,62(8):3270-3275.
[17]、G E Armah,S Nishikawa,S Miki,Y Omata,T Nakabayashi,K Tomita.Conformation and immunogenicity of engineered repeating segment of the circumsporozoite surface protein of Plasmodium falciparum[J].Molecular and biochemical parasitology,1990,38(1):135-140.
[18]、R Anker,F Zavala,B A Pollok.VH and VL region structure of antibodies that recognize the (NANP)3 dodecapeptide sequence in the circumsporozoite protein of Plasmodium falciparum[J].European journal of immunology,1990,20(12):2757-2761.
[19]、P Caspers,R Gentz,H Matile,J R Pink,F Sinigaglia.The circumsporozoite protein gene from NF54, a Plasmodium falciparum isolate used in malaria vaccine trials[J].Molecular and biochemical parasitology,1989,35(2):185-189.
[20]、E H Nardin,P J Barr,H L Gibson,W E Collins,R S Nussenzweig,V Nussenzweig.Induction of sporozoite-specific memory cells in mice immunized with a recombinant Plasmodium vivax circumsporozoite protein[J].European journal of immunology,1987,17(12):1763-1767.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号