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During feeding by infected mosquitoes, malaria sporozoites are injected into the host's bloodstream and enter hepatocytes within minutes. The remarkable target cell specificity of this parasite may be explained by the presence of receptors for the region II-plus of the circumsporozoite protein (CS) on the basolateral domain of the plasma membrane of hepatocytes. We have now identified these receptors as heparan sulfate proteoglycans (HSPG). The binding of CS to the receptors is abolished by heparitinase treatment, indicating that the recognition of region II-plus is via the glycosaminoglycan chains. We have purified and partially characterized the CS-binding HSPGs from HepG2 cells. They have a molecular weight of 400,000-700,000, are tightly associated with the plasma membrane, and are released from the cell surface by very mild trypsinization, a property which the CS receptors share with the syndecan family of proteoglycans.

We have investigated the pattern of acquired immune responses to the major surface protein of Plasmodium falciparum merozoites (gp 190, PfMSP1) in a malaria endemic population in West Africa. A prospective longitudinal study in 3- to 8-year-old children was conducted to examine the relationship between naturally acquired immune responses to PfMSP1 and subsequent susceptibility to malaria infection and clinical disease. A population cross-sectional survey was performed to investigate changes in immune response with age. The prevalence and concentration of antibodies to all regions of the molecule increased with age with the highest prevalence of antibodies being detected against regions of the molecule which are highly conserved between parasite isolates. In vitro lympho-proliferation and interferon-gamma production in response to recombinant proteins representing polymorphic regions of the molecule also increased with age. Interestingly, proliferative responses to some regions of the molecule, including some highly conserved sequences, were highest in young children and decreased markedly with increasing age. Significant associations were observed between antibody and lymphoproliferative responses to proteins from the C terminus of the molecule and resistance to episodes of fever associated with high parasitaemia in partially immune children. In addition, high concentrations of antibodies to a conserved region close to the N terminus of PfMSP1 were also significantly associated with protection.

Monoclonal antibodies, raised against a purified GABAA/benzodiazepine receptor complex from bovine cerebral cortex, have been used to visualize the cellular and subcellular distribution of receptorlike immunoreactivity in the rat CNS, cat spinal cord, and bovine and postmortem human brain. Two different antibodies have been used for these studies; bd-17 recognizes the beta-subunit (Mr 55 kDa) in all the species tested, whereas bd-24 recognizes the alpha-subunit (Mr 50 kDa) of bovine and human but not rat and cat tissues. In bovine and human brain, both antibodies produced very similar staining patterns, indicating a homogeneous receptor composition, at least in the brain areas investigated. The general distribution and density of receptor antigenic sites in all tissues studied were very similar to that of benzodiazepine binding sites radiolabeled with 3H-Ro 15-1788 and of glutamate decarboxylase (GAD)-stained nerve terminals. The results demonstrate a very high receptor density (around neuronal cell bodies and processes or less discretely distributed) in the rat olfactory bulbs, cerebral cortex, ventral pallidum, islands of Calleja, globus pallidus, hippocampus, dentate gyrus, substantia nigra, geniculate nuclei, inferior colliculus, cerebellum, reticular formation, spinal cord, and retina. In contrast, no receptors could be detected in white matter, pineal, pituitary, adrenals, and superior cervical ganglia. Only among the cerebellar layers did we observe a conspicuous difference between the staining intensity and the radiolabeling. In bovine and postmortem human brain, e.g., hippocampus, dentate gyrus, cerebral cortex, and substantia nigra, the same close correlation between the immunohistochemical and radiohistochemical findings was observed. At the electron microscopic level, the immune reaction product in the rat substantia nigra and globus pallidus, for example, was localized to pre- and postsynaptic membranes of axodendritic and axosomatic synapses. Whether the presynaptic labeling represents GABA autoreceptors is discussed. In the near future, the monoclonal antibodies will be used in double-labeling experiments with GAD to identify those GABAergic projections that are modulated by benzodiazepine minor tranquillizers. Furthermore, they could also be used, in studies of postmortem human brain, to diagnose receptor dysfunction possibly associated with CNS disorders such as epilepsy.