Research

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

Tonia Woodberry¹ , Alberto Pinzon-Charry² , Kim A Piera¹ , Yawalak Panpisutchai² , Christian R Engwerda² , Denise L Doolan² , Ervi Salwati³ , Enny Kenangalem⁴ , Emiliana Tjitra³ , Ric N Price^1,5 , Michael F Good² and Nicholas M Anstey¹

¹  International Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia

²  The Queensland Institute of Medical Research, Brisbane, Australia

³  National Institute of Health Research and Development, Ministry of Health, Jakarta, Indonesia

⁴  National Institute of Health Research and Development-Menzies School of Health Research Research Program and District Health Authority, Timika, Papua, Indonesia

⁵  Centre for Vaccinology & Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford, UK

author email corresponding author email

Malaria Journal 2009, 8:122doi:10.1186/1475-2875-8-122

Published:	7 June 2009

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.