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Peripheral blood mononuclear cells (PBM) from a patient who had lived in a malarial-endemic area were cultured in the presence of malarial antigens (a lysate of Plasmodium-infected erythrocytes). Responding cells were grown in IL-2-containing medium and then cloned, and subsequently subcloned, in the presence of phytohemagglutinin and allogeneic irradiated PBM. Ten clones were specific for malarial antigens. They proliferated in response to P. falciparum extract, but not to a lysate of uninfected erythrocytes. The response was HLArestricted. All the clones tested responded to lysates of cells infected with parasites of either African or Asian origin. Six clones had the T4+ /T8phenotype and four the T4-/T8+ phenotype. Two of the T4+ clones recognised a parasite antigen of apparent mol. wt. -50 000. All of the clones tested produced 'y-interferon following antigen stimulation.

We have examined T cell recognition of a recombinant polypeptide (190L), corresponding to a 175-amino-acid-long conserved region of the major surface antigen (p190) of Plasmodium falciparum merozoites. We show that 190L contains a variety of T cell epitopes, and can be recognized in association with many different MHC class II molecules, including HLA-DR, DP, and DQ antigens. Most of the epitope-containing peptides are able to bind to more than one DR, and a single DR molecule can bind to different peptides. These findings, together with the fact that humans are generally heterozygous at the DR, DQ, and DP beta chain loci, suggest that MHC restriction should not be a major constraint in the development of malaria subunit vaccines.

This report describes the isolation, and the phenotypic and functional characterization of Plasmodium falciparum-specific human T lymphocyte clones (TLC) obtained from 2 acutely infected and 4 clinically immune donors. Approximately one third of the TLC obtained from the acutely infected patients had the phenotype CD8+/CD4-. No such clones were obtained from the clinically immune donors. P. falciparum-specific, major histocompatibility complex-restricted CD8+ clones can lyse unrelated tumor cell targets in the presence of anti-CD3 antibodies, suggesting that these clones have cytotoxic potential. Conversely no killing was obtained with two CD4+ P. falciparum-specific TLC, even in the presence of anti-CD3 antibody, In addition the helper function of a CD4+ clone was demonstrated in a T/B cell cooperation system.

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