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

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...

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Asıl Yazarlar: Woodberry, T, Pinzon-Charry, A, Piera, K, Panpisutchai, Y, Engwerda, C, Doolan, D, Salwati, E, Kenangalem, E, Tjitra, E, Price, R, Good, M, Anstey, N
Materyal Türü: Journal article
Dil:English
Baskı/Yayın Bilgisi: BioMed Central 2009
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author Woodberry, T
Pinzon-Charry, A
Piera, K
Panpisutchai, Y
Engwerda, C
Doolan, D
Salwati, E
Kenangalem, E
Tjitra, E
Price, R
Good, M
Anstey, N
author_facet Woodberry, T
Pinzon-Charry, A
Piera, K
Panpisutchai, Y
Engwerda, C
Doolan, D
Salwati, E
Kenangalem, E
Tjitra, E
Price, R
Good, M
Anstey, N
author_sort Woodberry, T
collection OXFORD
description 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.
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spelling oxford-uuid:b0b3aabe-8a89-48fb-add9-48c0bfb305372022-03-27T03:58:22ZHuman T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) in acute malaria.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b0b3aabe-8a89-48fb-add9-48c0bfb30537EnglishSymplectic Elements at OxfordBioMed Central2009Woodberry, TPinzon-Charry, APiera, KPanpisutchai, YEngwerda, CDoolan, DSalwati, EKenangalem, ETjitra, EPrice, RGood, MAnstey, N 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.
spellingShingle Woodberry, T
Pinzon-Charry, A
Piera, K
Panpisutchai, Y
Engwerda, C
Doolan, D
Salwati, E
Kenangalem, E
Tjitra, E
Price, R
Good, M
Anstey, N
Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) in acute malaria.
title Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) in acute malaria.
title_full Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) in acute malaria.
title_fullStr Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) in acute malaria.
title_full_unstemmed Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) in acute malaria.
title_short Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) in acute malaria.
title_sort human t cell recognition of the blood stage antigen plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase hgxprt in acute malaria
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