Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) in acute malaria

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Title Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) in acute malaria
Author Woodberry, Tonia; Pinzon-Charry, Alberto; Piera, Kim A; Panpisutchai, Yawalak; Engwerda, Christian R; Doolan, Denise L; Salwati, Ervi; Kenangalem, Enny; Tjitra, Emiliana; Price, Ric N; Good, Michael Francis; Anstey, Nicholas M
Journal Name Malaria Journal
Year Published 2009
Place of publication United Kingdom
Publisher BioMed Central Ltd.
Abstract Background The Plasmodium purine salvage enzyme, hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) can protect mice against Plasmodium yoelii pRBC challenge in a T cell-dependent manner and has, therefore, been proposed as a novel vaccine candidate. It is not known whether natural exposure to Plasmodium falciparum stimulates HGXPRT T cell reactivity in humans. Methods PBMC and plasma collected from malaria-exposed Indonesians during infection and 7–28 days after anti-malarial therapy, were assessed for HGXPRT recognition using CFSE proliferation, IFNγ ELISPOT assay and ELISA. Results HGXPRT-specific T cell proliferation was found in 44% of patients during acute infection; in 80% of responders both CD4+ and CD8+ T cell subsets proliferated. Antigen-specific T cell proliferation was largely lost within 28 days of parasite clearance. HGXPRT-specific IFN-γ production was more frequent 28 days after treatment than during acute infection. HGXPRT-specific plasma IgG was undetectable even in individuals exposed to malaria for at least two years. Conclusion The prevalence of acute proliferative and convalescent IFNγ responses to HGXPRT demonstrates cellular immunogenicity in humans. Further studies to determine minimal HGXPRT epitopes, the specificity of responses for Plasmodia and associations with protection are required. Frequent and robust T cell proliferation, high sequence conservation among Plasmodium species and absent IgG responses distinguish HGXPRT from other malaria antigens.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1186/1475-2875-8-122
Volume 8
Page from 1
Page to 10
ISSN 1475-2875
Date Accessioned 2011-07-14
Date Available 2011-08-12T06:21:22Z
Language en_AU
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Medical Microbiology
URI http://hdl.handle.net/10072/39959
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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