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Fine Specificity of Neonatal Lymphocytes to an Abundant Malaria Blood-Stage Antigen: Epitope Mapping of Plasmodium falciparum MSP1₃₃¹

Indu Malhotra^2,*, Alex N. Wamachi, Peter L. Mungai^*, Elton Mzungu, Davy Koech, Eric Muchiri, Ann M. Moormann^* and Christopher L. King^2,*,

^* Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH 44106; Kenya Medical Research Institute, Nairobi, Kenya; Division of Vector Borne Diseases, Nairobi, Kenya; and Department of Veterans Affairs Medical Center, Cleveland, OH 44106

Cord blood T cells have been reported to respond to a variety of exogenous Ags, including environmental allergens and various viruses and parasites, as demonstrated by enhanced proliferation and cytokine secretion. This finding is evidence that Ags in the maternal environment transplacentally prime and result in fetal development of memory T cells. Some studies suggest these neonatal T cell responses may arise by nonspecific activation of T cells that express TCRs with low binding affinity, thus lacking fine lymphocyte specificity. To address this question, we examined malaria Ag stimulation of human cord and adult blood mononuclear cells in samples from residents of a malaria endemic area in Kenya. We constructed overlapping 18-mer peptides derived from sequences contained in dimorphic alleles of the C-terminal 33-kDa fragment of Plasmodium falciparum merozoite protein 1. This study identified a dominant T cell epitope for one MSP1₃₃ allele (MAD20) and two T cell epitopes for the second allele (K1); these epitopes were nonoverlapping and allele specific. In a given donor, peptide-specific proliferation and IFN- secretion were highly concordant. However, IL-10 and IL-13 secretion were not correlated. Importantly, the fine specificity of lymphocyte proliferation and cytokine secretion in cord and adult blood mononuclear cells was similar. Cord blood cells obtained from malaria-infected pregnant women were 4-fold more likely to acquire a peptide-specific immune response. We conclude that the fetal malaria response functions in a fully adaptive manner and that this response may serve to help protect the infant from severe malaria during infancy.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Health and Human Services Grant AI064687 and by the Veterans Affairs Research Service.

² Address correspondence and reprint requests to Drs. Indu Malhotra and Christopher L. King, Case Western Reserve University, Wolstein Research Center Room 4132, 2103 Cornell Road, Cleveland, OH 44106. E-mail addresses: ijm{at}case.edu and cxk21{at}case.edu

³ Abbreviations used in this paper: CBMC, cord blood mononuclear cell; MSP1, merozoite surface protein 1; ssu, small subunit; SI, stimulation index.