Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) in acute malaria
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 n...
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ftdoajarticles:oai:doaj.org/article:5ee2cb56f18c4f00bc28c8fb0e80dec3 2023-05-15T15:09:43+02:00 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 Anstey Nicholas M 2009-06-01T00:00:00Z https://doi.org/10.1186/1475-2875-8-122 https://doaj.org/article/5ee2cb56f18c4f00bc28c8fb0e80dec3 EN eng BMC http://www.malariajournal.com/content/8/1/122 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-8-122 1475-2875 https://doaj.org/article/5ee2cb56f18c4f00bc28c8fb0e80dec3 Malaria Journal, Vol 8, Iss 1, p 122 (2009) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2009 ftdoajarticles https://doi.org/10.1186/1475-2875-8-122 2022-12-31T02:54:45Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 8 1 |
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Directory of Open Access Journals: DOAJ Articles |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 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 Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) in acute malaria |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
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. |
format |
Article in Journal/Newspaper |
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 |
author_facet |
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 |
author_sort |
Woodberry Tonia |
title |
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_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_sort |
human t cell recognition of the blood stage antigen plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (hgxprt) in acute malaria |
publisher |
BMC |
publishDate |
2009 |
url |
https://doi.org/10.1186/1475-2875-8-122 https://doaj.org/article/5ee2cb56f18c4f00bc28c8fb0e80dec3 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 8, Iss 1, p 122 (2009) |
op_relation |
http://www.malariajournal.com/content/8/1/122 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-8-122 1475-2875 https://doaj.org/article/5ee2cb56f18c4f00bc28c8fb0e80dec3 |
op_doi |
https://doi.org/10.1186/1475-2875-8-122 |
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Malaria Journal |
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8 |
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1 |
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1766340848908238848 |