Nature 360, 434 - 439 (03 December 1992); doi:10.1038/360434a0

Molecular analysis of the association of HLA-B53 and resistance to severe malaria

Adrian V. S. Hill^*, John Elvin^*, Anthony C. Willis^†, Michael Aidoo^‡, Catherine E. M. Allsopp^*, Frances M. Gotch^*, X. Ming Gao^*, Masafumi Takiguchis^§, Brian M. Greenwood^‡, Alain R. M. Townsend^*, Andrew J. McMichael^* & Hilton C. Whittle^‡

^*Molecular Immunology Group, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford 0X3 9DU, UK
^†MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford 0X1 3QU, UK
^‡Medical Research Council Laboratories, Fajara, Banjul, The Gambia, West Africa
^§Institute of Medical Sciences, University of Tokyo, Minato-ku, Tokyo 108, Japan

The protective association between the human leukocyte antigen HLA-B53 and severe malaria was investigated by sequencing of peptides eluted from this molecule followed by screening of candidate epitopes from pre-erythrocytic-stage antigens of Plasmodium falciparum in biochemical and cellular assays. Among malaria-immune Africans, HLA-B53-restricted cytotoxic T lymphocytes recognized a conserved nonamer peptide from liver-stage-specific antigen-1 (LSA-1), but no HLA-B53-restricted epitopes were identified in other antigens. These findings indicate a possible molecular basis for this HLA-disease association and support the candidacy of liver-stage-specific antigen-1 as a malaria vaccine component.

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