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Biomedical subjects

D Nikodem

Publications and source records attributed to D Nikodem.

4 recordsLinked to original sources
PubMed2000

Identification of a novel antigenic domain of Plasmodium falciparum merozoite surface protein-1 that specifically binds to human erythrocytes and inhibits parasite invasion, in vitro.

Merozoite surface protein 1 (MSP-1) of Plasmodium falciparum is a promising candidate for vaccine development against malaria. Identification of protective epitopes within MSP-1 is an important step towards the elucidation of mechanisms of parasitic invasion and for the creation of a multi-subunit vaccine. In this study, we show that a 115 amino acid region (p115MSP-1) within the p38 domain of MSP-1 can: (i) specifically bind to human erythrocytes, independent of glycophorin A; (ii) inhibit parasite invasion at significant levels, in vitro; and (iii) be recognized by human sera of individuals from malaria-endemic regions of Africa. More importantly, we also show that polyclonal antibodies specific to this region prevent parasite invasion at levels approaching 90%, in vitro. Our data illustrate that not only is p115MSP-1 involved in parasite recognition/invasion of human erythrocytes, but that this region is highly antigenic, producing high titer antibodies. The delineation of the role of MSP-1 in parasite invasion is an important component of the development of a multi-subunit malaria vaccine, and this study identifies a candidate antigen in this context.

Adolescent↗
PubMed1999

Glycosylation and proteolytic processing of 70 kDa C-terminal recombinant polypeptides of Plasmodium falciparum merozoite surface protein 1 expressed in mammalian cells.

The cDNAs that encode the 70 kDa C-terminal portion of Plasmodium falciparum merozoite surface protein 1 (MSP-1), with or without an N-terminal signal peptide sequence and C-terminal glycosylphosphatidylinositol (GPI) signal sequence of MSP-1, were expressed in mammalian cell lines via recombinant vaccinia virus. The polypeptides were studied with respect to the nature of glycosylation, localization, and proteolytic processing. The polypeptides derived from the cDNAs that contained the N-terminal signal peptide were modified with N -linked high mannose type structures and low levels of O -linked oligosaccharides, whereas the polypeptides from the cDNAs that lacked the signal peptide were not glycosylated. The GPI anchor moiety is either absent or present at a very low level in the polypeptide expressed from the cDNA that contained both the signal peptide and GPI signal sequences. Together, these data establish that whereas the signal peptide of MSP-1 is functional, the GPI anchor signal is either nonfunctional or poorly functional in mammalian cells. The polypeptides expressed from the cDNAs that contained the signal peptide were proteolytically cleaved at their C-termini, whereas the polypeptides expressed from the cDNAs that lacked the signal peptide were uncleaved. While the polypeptide expressed from the cDNA containing both the signal peptide and GPI anchor signal was truncated by approximately 14 kDa at the C-terminus, the polypeptide derived from the cDNA with only the signal peptide was processed to remove approximately 6 kDa, also from the C-terminus. Furthermore, the polypeptides derived from cDNAs that lacked the signal peptide were exclusively localized intra-cellularly, the polypeptides from cDNAs that contained the signal peptide were predominantly intracellular, with low levels on the cell surface; none of the polypeptides was secreted into the culture medium to a detectable level. These results suggest that N -glycosylation alone is not sufficient for the efficient extracellular transport of the recombinant MSP-1 polypeptides through the secretory pathway in mammalian cells.

Animals↗
PubMed1996

Active repression of major histocompatibility complex class I genes in a human neuroblastoma cell line.

Human neuronal cells express neither major histocompatibility complex (MHC) class I RNA nor cell surface molecules but can be induced to do so by various cytokines. In the present studies, we report that expression of MHC class I in a neuroblastoma cell line, CHP-126, is actively repressed. This repression is mediated by the combined effects of a series of upstream silencer elements. Removal of the silencers reveals not only an active promoter element but also the presence of an active enhancer. Four silencers have been identified and shown to have distinct sequences, binding factors, and patterns of function. One element is located between -724 and -697 base pairs (bp) and corresponds to a silencer involved in tissue-specific regulation of class I gene expression. Three additional elements occur between -503 and -402 bp. One of these corresponds to a c-jun responsive element. Neither of the remaining elements corresponds to DNA sequences known to regulate expression of other genes. These data demonstrate that MHC class I expression normally is actively repressed in neuronal cells and suggest a model of rapid and specific triggering of class I in neuronal cells in response to infection.

Base Sequence↗