期刊论文详细信息
Malaria Journal
Identification and localization of minimal MHC-restricted CD8+ T cell epitopes within the Plasmodium falciparum AMA1 protein
Research
Bart Faber1  Edmond Remarque1  Michael R Hollingdale2  C Richter King3  Joseph T Bruder3  Yohan Kim4  Bjoern Peters4  Alessandro Sette4  Denise L Doolan5  Ilin Chuang6  Cindy Tamminga6  Martha Sedegah6  David Regis6  Thomas L Richie6  Harini Ganeshan7  Fouzia Farooq7  Jennylynn Lejano7  Glenna Banania7  Maria Belmonte7  Renato Sayo7  Esteban Abot7  Shannon McGrath8  Christian F Ockenhouse8 
[1] Biomedical Primate Research Centre, Rijswijk, The Netherlands;Consultant to the USMMVP, Malaria Department, NMRC, 20910, Silver Spring, MD, USA;GenVec, 20878, Gaithersburg, MD, USA;La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA;Queensland Institute of Medical Research, Brisbane, Queensland, Australia;U.S. Military Malaria Vaccine Program, Naval Medical Research Center, 503 Robert Grant Avenue, 20910-7500, Silver Spring, MD, USA;U.S. Military Malaria Vaccine Program, Naval Medical Research Center, 503 Robert Grant Avenue, 20910-7500, Silver Spring, MD, USA;Henry M. Jackson Foundation for the Advancement of Military Medicine, 20852, Rockville, MD, USA;U.S. Military Malaria Vaccine Program, Walter Reed Army Institute of Research, 20910, Silver Spring, MD, USA;
关键词: Peripheral Blood Mononuclear Cell;    Cell Epitope;    ELISpot Assay;    Peptide Pool;    Intracellular Cytokine Staining;   
DOI  :  10.1186/1475-2875-9-241
 received in 2010-04-09, accepted in 2010-08-24,  发布年份 2010
来源: Springer
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【 摘 要 】

BackgroundPlasmodium falciparum apical membrane antigen-1 (AMA1) is a leading malaria vaccine candidate antigen that is expressed by sporozoite, liver and blood stage parasites. Since CD8+ T cell responses have been implicated in protection against pre-erythrocytic stage malaria, this study was designed to identify MHC class I-restricted epitopes within AMA1.MethodsA recombinant adenovirus serotype 5 vector expressing P. falciparum AMA1 was highly immunogenic when administered to healthy, malaria-naive adult volunteers as determined by IFN-γ ELISpot responses to peptide pools containing overlapping 15-mer peptides spanning full-length AMA1. Computerized algorithms (NetMHC software) were used to predict minimal MHC-restricted 8-10-mer epitope sequences within AMA1 15-mer peptides active in ELISpot. A subset of epitopes was synthesized and tested for induction of CD8+ T cell IFN-γ responses by ELISpot depletion and ICS assays. A 3-dimensional model combining Domains I + II of P. falciparum AMA1 and Domain III of P. vivax AMA1 was used to map these epitopes.ResultsFourteen 8-10-mer epitopes were predicted to bind to HLA supertypes A01 (3 epitopes), A02 (4 epitopes), B08 (2 epitopes) and B44 (5 epitopes). Nine of the 14 predicted epitopes were recognized in ELISpot or ELISpot and ICS assays by one or more volunteers. Depletion of T cell subsets confirmed that these epitopes were CD8+ T cell-dependent. A mixture of the 14 minimal epitopes was capable of recalling CD8+ T cell IFN-γ responses from PBMC of immunized volunteers. Thirteen of the 14 predicted epitopes were polymorphic and the majority localized to the more conserved front surface of the AMA1 model structure.ConclusionsThis study predicted 14 and confirmed nine MHC class I-restricted CD8+ T cell epitopes on AMA1 recognized in the context of seven HLA alleles. These HLA alleles belong to four HLA supertypes that have a phenotypic frequency between 23% - 100% in different human populations.

【 授权许可】

Unknown   
© Sedegah et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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