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Identification of frequently recognized dimorphic T-cell epitopes in plasmodium falciparum merozoite surface protein-1 in West and East Africans: lack of correlation of immune recognition and allelic prevalence.

E A LeeInstitute of Molecular Medicine, Nuffield Department Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom. elee@molbiol.ox.ac.uk

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K L FlanaganInstitute of Molecular Medicine, Nuffield Department Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom. elee@molbiol.ox.ac.uk

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K OdhiamboInstitute of Molecular Medicine, Nuffield Department Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom. elee@molbiol.ox.ac.uk

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W H ReeceInstitute of Molecular Medicine, Nuffield Department Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom. elee@molbiol.ox.ac.uk

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C PotterInstitute of Molecular Medicine, Nuffield Department Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom. elee@molbiol.ox.ac.uk

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R BaileyInstitute of Molecular Medicine, Nuffield Department Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom. elee@molbiol.ox.ac.uk

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K MarshInstitute of Molecular Medicine, Nuffield Department Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom. elee@molbiol.ox.ac.uk

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M PinderInstitute of Molecular Medicine, Nuffield Department Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom. elee@molbiol.ox.ac.uk

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A V HillInstitute of Molecular Medicine, Nuffield Department Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom. elee@molbiol.ox.ac.uk

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M PlebanskiInstitute of Molecular Medicine, Nuffield Department Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom. elee@molbiol.ox.ac.uk

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The merozoite surface protein-1 (MSP1) is the most studied malaria blood-stage vaccine candidate. Lymphokines such as interferon gamma (IFN-gamma) and interleukin 4 (IL-4) may mediate blood-stage specific protection. Here we identify Plasmodiumfalciparum MSP1 T-cell epitopes capable of rapid induction of IFN-gamma and/or IL-4 from peripheral blood mononuclear cells of East and West African donors. Both allelic forms of these novel MSP1 T-cell epitopes were stimulatory. An unusually high numbers of Gambian responders (> 80%) to these epitopes were observed, suggesting that MSPI reactivity may have been underestimated previously in this population. Surprisingly, IFN-gamma responses to allelic T-cell epitopes failed to correlate with differential antigenic exposure in The Gambia compared to Kenya. These results suggest an unexpected level of immunoregulation of IFN-gamma response with variable allelic T-cell reactivity independent of the level of antigenic exposure. Further analysis of the mechanisms determining this response pattern may be required if vaccines are to overcome this allelic reactivity bias in malaria-exposed populations.

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