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 (122). pp. 1-10.

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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.

Item ID: 42731
Item Type: Article (Refereed Research - C1)
Additional Information:

© Woodberry et al; licensee BioMed Central Ltd. 2009

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.

ISSN: 1475-2875
Funders: National Health and Medical Research Council (NHMRC), Welcome Trust (WT)
Projects and Grants: NHMRC 290208, NHMRC 49660, NHMRC ICRG 283321, WT ICRG GR071614MA
Date Deposited: 24 Mar 2016 01:07
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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