Identification of a heat shock-like antigen in P.falciparum, related to the heat shock protein 90 family

Abstract

Previous reports have shown that squirrel monkeys vaccinated with a protein fraction of 75Kd prepared from culture forms of the Palo Alto FUP strain of P.falciparum, showed a high degree of protection which correlated with the presence of antibodies essentially against parasite polypeptides of 9OKd and 72Kd (1,2). The 72 Kd polypeptide was identified as a nmember,of the P.falciparum heat shock 70.family.(3-6). Two other related proteins of the heat shock 70 family have also been identified (7-8). Using a polyclonal immune sera against the 9OKd region from P.falciparum, several cDNA clones were isolated from an expression library constructed in the pUC9 vector. Interestingly, the deduced amino-acid sequence of clone C27 shows significant homology with proteins from the heat shock 90 family ( 50-56%)(9-10) and lower homology with the Glucose regulated protein GRP94 of mammalian cells (42%)(11). This antigen thus represent the fourth Hsp-like protein expressed by P.falciparum.

Heat-inducible ATP-binding proteins of Candida albicans are recognized by sera of infected patients

“…This hypothesis is supported by data with squirrel monkeys infected by Plasmodium falciparum. Immunization of squirrel monkeys with hsp90 of P. falciparum induces a protective humoral immunity against a future infection with P. falciparum (Dubois et al, 1984;Jendoubi & Bonnefoy, 1988). The question of whether these antibodies against the heat-shock proteins of C. albicans really have a role in the host immune defence, as with antibodies to the 47 kDa protein (Matthews & Burnie, 1992), has to be studied in more detail.…”

“…Antibodies against heat-shock proteins have been found in different parasitic infections, not only against invasive organisms living in the bloodstream like Schistosoma mansoni (Hedstrom et al, 1987) or Brugia (Selkirk et al, 1989), but also against intracellular parasites like Plasmodium or Mycobacterium (Bianco et al, 1986;Young et al, 1988;Jendoubi & Bonnefoy, 1988). In most cases the presence of antibodies reacting with heat-shock proteins has been demonstrated by sequencing cDNA clones isolated by antibody screening of expression libraries and observing sequence homology with heat-shock proteins (Bianco et al, 1986;Hedstrom et al, 1987;Jendoubi & Bonnefoy, 1988;Selkirk et al, 1989). We aimed to determine whether other heat-shock proteins of C. albicans are also recognized as antigens in human candidiasis, especially mucosal infections.…”

Host Chaperones Are Recruited in Membrane-bound Complexes byPlasmodium falciparum

“…We cannot, however, rule out the possibility that some amount of hostHsp90 is tightly associated with the parasite. It must be mentioned here that, based on immunofluorescence analysis (14), it has been suggested that some PfHsp90 is in the parasitophorous vacuole. Our results do not rule out this possibility.…”

“…Monoclonal antibody to PfHRP1 (mAb 89) was a gift from Dr. D. Taylor. C27 clone expressing the C-terminal 193 residues of PfHsp90 was a gift from Dr. S. Bonnefoy (Pasteur Institute, Paris) (14,27). Antibody to PfBiP was a kind gift from Dr. Nirbhay Kumar.…”

“…The involvement of molecular chaperones in the erythrocyte cytoplasm is often suggested in facilitating the transport and assembly of proteins destined for the plasma membranes (10 -12). Several candidate chaperones belonging to the heat shock protein family have been identified in the parasite (13)(14)(15)(16)(17)(18)(19); however, only limited information is available about their localizations and possible functions. Most importantly, so far there is no evidence of a bona fide chaperone of parasite origin being present in the erythrocyte cytoplasm.…”