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

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 F. and Anstey, Nicholas M. (2009). Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) in acute malaria. Malaria Journal,8(1):122-131.

Document type: Journal Article
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IRMA ID 10291xPUB7
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 F.
Anstey, Nicholas M.
Journal Name Malaria Journal
Publication Date 2009
Volume Number 8
Issue Number 1
ISSN 1475-2875   (check CDU catalogue open catalogue search in new window)
Start Page 122
End Page 131
Total Pages 10
Place of Publication London, U.K.
Publisher BioMed Central Ltd.
HERDC Category C1 - Journal Article (DEST)
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, IFNgamma 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-gamma 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 IFNgamma 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.
DOI http://dx.doi.org/10.1186/1475-2875-8-122   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)


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