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1.
J Infect Dis ; 182(5): 1486-96, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11023472

ABSTRACT

A multiple antigen peptide (MAP) malaria vaccine containing minimal Plasmodium falciparum circumsporozoite protein repeat epitopes was assessed for safety and immunogenicity in volunteers of known class II genotypes. The MAP/alum/QS-21 vaccine formulation elicited high levels of parasite-specific antibodies in 10 of 12 volunteers expressing DQB1*0603, DRB1*0401, or DRB1*1101 class II molecules. In contrast, volunteers of other HLA genotypes were low responders or nonresponders. A second study of 7 volunteers confirmed the correlation of class II genotype and high responder phenotype. This is the first demonstration in humans that a peptide vaccine containing minimal T and B cell epitopes composed of only 5 amino acids (N, A, V, D, and P) can elicit antibody titers comparable to multiple exposures to irradiated P. falciparum-infected mosquitoes. Moreover, the high-responder phenotypes were predicted by analysis of peptide/HLA interactions in vitro, thus facilitating the rational design of epitope-based peptide vaccines for malaria, as well as for other pathogens.


Subject(s)
Antibodies, Protozoan/biosynthesis , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Malaria Vaccines/immunology , Plasmodium falciparum/immunology , Vaccines, Synthetic/immunology , Adult , Animals , Cohort Studies , Female , Genotype , HLA-DQ beta-Chains , HLA-DRB1 Chains , Humans , Male , Saponins/pharmacology
2.
Vaccine ; 18(5-6): 531-9, 1999 Oct 14.
Article in English | MEDLINE | ID: mdl-10519944

ABSTRACT

The safety and immunogenicity of 2 yeast-derived, blood-stage malaria vaccines were evaluated in a phase l trial. Healthy adults were given 2 or 3 doses of alum-adsorbed vaccine containing the 19 kDa carboxy-terminal fragment of the merozoite surface protein-1 (MSP-1(19)) derived from the 3D7 or the FVO strain of Plasmodium falciparum fused to tetanus toxoid T-helper epitopes P30 and P2. The first 2 doses of MSP-1(19) were well tolerated. Hypersensitivity reactions occurred in 3 subjects after the third dose of MSP-1(19), including bilateral injection site reactions in 2 (one with generalized skin rash), and probable histamine-associated hypotension in 1. Serum antibody responses to MSP-1(19) occurred in 5/16, 9/16 and 0/8 subjects given 20 microg of MSP-1(19), 200 microg of MSP-1(19), and control vaccines (hepatitis B or Td), respectively. Both MSP-1(19) vaccines were immunogenic in humans, but changes in formulation will be necessary to improve safety and immunogenicity profiles.


Subject(s)
Epitopes, T-Lymphocyte , Malaria Vaccines/immunology , Merozoite Surface Protein 1/immunology , Peptide Fragments/immunology , Plasmodium falciparum/immunology , T-Lymphocytes, Helper-Inducer/immunology , Tetanus Toxoid/immunology , Vaccines, Synthetic/immunology , Adolescent , Adult , Animals , Antibodies, Protozoan/blood , Humans , Lymphocyte Activation , Malaria Vaccines/adverse effects , Middle Aged , Skin Tests
3.
Leukemia ; 9(8): 1373-81, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7643627

ABSTRACT

Treatment of HL-60 with phorbol myristate acetate (PMA) for 30 min, or all-trans retinoic acid (RA) for 60 min, results in hyperphosphorylation (3-5x) of topoisomerase II (p170, topo II) in vivo. RA and PMA activate a coprecipitating kinase, respectively inducing 1.6 and 2.7-fold increases in phosphorylation of topo II in immunoprecipitates. The activity of the co-precipitating kinase is inhibited by heparin and unlabelled GTP suggesting that casein kinase II (CKII) is, at least in part, responsible for the topo II hyperphosphorylation in response to differentiation signals. Although following dephosphorylation of the enzyme with alkaline phosphatase there was virtual abrogation of activity, the differentiation associated hyperphosphorylation had little impact on the decatenation activity of topo II in nuclear extracts. There were, however detectable changes in topo II function in vivo which affected the formation of the etoposide stabilised cleavable complex, but only after PMA treatment. PMA resulted in a rapid reduction in etoposide induced cleavage, 30 min treatment with PMA reducing cleavage by 20%. However, treatment with RA for 1 or 2 h when hyperphosphorylation was maximal did not affect cleavage. Immunoband depletion assays suggested that differentiation associated changes in chromatin structure rather than alterations in the enzyme per se are responsible for the reduction in cleavable complex formation following PMA treatment. Etoposide cytotoxicity was significantly reduced following just 30 min PMA treatment, but not reduced and even possibly enhanced by retinoic acid treatment. These findings are relevant not only to the dissection of the role of topo II in differentiation but also to its exploitation as a therapeutic target.


Subject(s)
DNA Topoisomerases, Type II/metabolism , Etoposide/toxicity , Isoenzymes/metabolism , Phorbol Esters/pharmacology , Tretinoin/pharmacology , Antigens, Neoplasm , Casein Kinase II , Cell Differentiation/drug effects , Cell Nucleus/metabolism , Cell Survival/drug effects , DNA-Binding Proteins , Enzyme Activation/drug effects , Humans , In Vitro Techniques , Leukemia, Myeloid/pathology , Peptide Mapping , Phosphorylation , Protein Serine-Threonine Kinases/metabolism , Time Factors , Tumor Cells, Cultured
4.
Science ; 266(5192): 1792, 1994 Dec 16.
Article in English | MEDLINE | ID: mdl-7864993

ABSTRACT

In our report "Activation of Raf as a result of recruitment to the plasma membrane" (3 June, p. 1463) (1), panels E and F of figure 1 on page 1464 were incorrect. The correct photographs appear below. In addition, the [See figure in the PDF file] second sentence of the legend to figure 1 should have read, "The Raf constructs were tagged at the COOH-terminus with a Glu-Glu epitope (MEYMPME) (24) for c-Raf, or at the NH(2)-terminus with both the Glu-Glu and the Myc (MEQKLISEEDL) (23) epitopes for RafCAAX"; the next-to-the-last sentence of the legend to figure 1 should have read, "The c-Raf constructs in (A through D) are Glu-Glu-tagged and were detected by using an anti Glu-Glu antibody, and the RafCAAX and Raf6QCAAX constructs used in E and F were detected by using the antibody to Raf COOH-terminal peptide"; and the third sentence of note 26 should have read, "After blocking with 5% milk in phosphate-buffered saline (M-PBS), cells were incubated with a mouse monoclonal antibody to Glu-Glu or a rabbit polyclonal antibody to a 20-amino acid COOH-terminal peptide of Raf-1 (Santa Cruz Biotechnology, Santa Cruz, California), washed, and incubated with donkey antibodies to mouse or rabbit IgG combined with Texas Red (Jackson) in M-PBS, washed, and mounted in FITC-Guard (Testog)."


Subject(s)
Malaria Vaccines , Research , Government Agencies , Humans , International Cooperation , National Institutes of Health (U.S.) , United States , World Health Organization
5.
Science ; 265(5177): 1401-4, 1994 Sep 02.
Article in English | MEDLINE | ID: mdl-7521064

ABSTRACT

The development of vaccines to prevent infectious diseases has been one of the most important contributions of biomedical science. Recent advances in the basic sciences are now fueling the development of a new generation of vaccines that will be based on rational design approaches. Two factors are making this possible: an improved understanding of the microbial factors required for virulence and the nature of the immune response to infection. The status of new vaccine technologies is summarized here.


Subject(s)
Vaccines, Combined , Vaccines, Conjugate , Vaccines, Synthetic , Adjuvants, Immunologic , Animals , Antigens/genetics , Antigens/immunology , Cytokines/immunology , DNA/genetics , Epitopes/immunology , Humans , ISCOMs/immunology , Vaccination , Vaccines, Combined/immunology , Vaccines, Conjugate/immunology , Vaccines, Synthetic/immunology
6.
Semin Cell Biol ; 4(5): 323-33, 1993 Oct.
Article in English | MEDLINE | ID: mdl-8257784

ABSTRACT

Infective trypomastigote stages of the obligate intracellular protozoan parasite Trypanosoma cruzi are capable of entering virtually any mammalian cell in vitro. Entry is a complex process, involving initial parasite attachment to surface moieties of the target cell, internalization of the parasite via formation of a vacuole, and finally disruption of the vacuolar membrane to permit access of the parasite to the host cell cytoplasm. Attachment requires parasite metabolic energy. At sites of parasite entry recruitment of host cell lysosomes may occur, and lysosomal membrane components contribute prominently to formation of the parasitophorous vacuole. Parasite escape from the vacuole depends upon vacuolar acidification and is mediated by the coordinated action of a parasite-derived neuraminidase/trans-sialidase that is capable of desialylating host-derived vacuolar membrane constituents, and a parasite-derived trans-membrane pore-forming protein. Dissection of the entry process at both the organellar and molecular level is providing fundamental and complementary insights into microbial pathogenesis and cell biology.


Subject(s)
Chagas Disease/parasitology , Trypanosoma cruzi/physiology , Animals , Cell Adhesion , Cells, Cultured , Chagas Disease/pathology , Cytoplasm/parasitology , Endocytosis , Humans , Lysosomes/metabolism , Vacuoles
7.
Infect Immun ; 61(9): 3656-63, 1993 Sep.
Article in English | MEDLINE | ID: mdl-7689538

ABSTRACT

Resistance to complement-mediated lysis in Trypanosoma cruzi is due to the expression of complement-regulatory factors by the virulent developmental forms of this protozoan parasite. An 87- to 93-kDa molecule, which we have termed T-DAF (trypomastigote decay-accelerating factor), is present on the surface of the parasite and inhibits complement activation in a manner functionally similar to the mammalian complement regulatory component, decay-accelerating factor. In this report, we characterized monospecific polyclonal and monoclonal antibodies which were obtained from mice and rabbits immunized with fast protein liquid chromatography-purified T-DAF. These polyclonal antibodies were shown to inhibit T-DAF activity and were capable of inducing lysis of the parasites. Both the polyclonal and monoclonal antibodies were used to screen a cDNA expression library prepared from T. cruzi trypomastigote mRNA. From this library, we obtained a partial lambda gt11 cDNA clone which showed genetic and functional similarity to the human C3 convertase inhibitor DAF (A. Nicholson-Weller, J. Burge, D. T. Fearon, P. F. Weller, and K. F. Austen, J. Immunol. 129:184-189, 1982).


Subject(s)
Antigens, CD/genetics , Antigens, Protozoan , Cloning, Molecular , Complement Inactivator Proteins/genetics , Membrane Glycoproteins/genetics , Protozoan Proteins , Trypanosoma cruzi/immunology , Amino Acid Sequence , Animals , Antibodies, Monoclonal/immunology , Antigens, CD/immunology , Antigens, CD/physiology , Base Sequence , CD55 Antigens , DNA/genetics , DNA/isolation & purification , Humans , Immune Sera/immunology , Membrane Glycoproteins/immunology , Membrane Glycoproteins/physiology , Mice , Molecular Sequence Data , Rabbits , Trypanosoma cruzi/genetics
8.
Trop Med Parasitol ; 44(2): 91-4, 1993 Jun.
Article in English | MEDLINE | ID: mdl-7690153

ABSTRACT

In this study we describe a simple and rapid method that uses sulfo-N-hydroxy-succinimidobiotin (sulfo-NHS-biotin) to label Trypanosoma cruzi surface proteins stably without significant loss of biological function. Efficient labelling can be obtained with as little as a 5 minute incubation of parasites in an appropriate concentration of sulfo-NHS-biotin at 4 degrees C. After labelling under these conditions, biotinylated parasites exhibited levels of motility, viability, and in vivo infectivity comparable to those seen with unlabelled control parasites. Moreover, the biological activity of T-DAF, a complement regulatory protein found on the parasite surface, was unaffected when biotinylated under these conditions. Biotinylated surface proteins can be easily detected in a variety of non-radioactive assays employing conjugated streptavidin as a developer. Compared to alternative techniques of surface labelling described in the literature, this method offers better preservation of biological function as well as greater ease of use and safety.


Subject(s)
Affinity Labels , Biotin/analogs & derivatives , Membrane Proteins/chemistry , Protozoan Proteins/chemistry , Succinimides , Trypanosoma cruzi/drug effects , Animals , Antigens, CD/biosynthesis , Antigens, CD/isolation & purification , Biotin/pharmacology , Blotting, Western , CD55 Antigens , Complement Inactivator Proteins/biosynthesis , Complement Inactivator Proteins/isolation & purification , Electrophoresis, Polyacrylamide Gel , Membrane Glycoproteins/biosynthesis , Membrane Glycoproteins/isolation & purification , Membrane Proteins/biosynthesis , Mice , Protozoan Proteins/biosynthesis , Succinimides/pharmacology , Time Factors , Trypanosoma cruzi/chemistry , Trypanosoma cruzi/physiology
9.
J Eukaryot Microbiol ; 40(2): 207-13, 1993.
Article in English | MEDLINE | ID: mdl-8461894

ABSTRACT

Developmental preadaptation of virulent stages of Trypanosoma cruzi correlates with their ability to survive and establish infection in mammalian hosts. Infective trypomastigote stages must first preadapt to survival in the extracellular milieu and then to the rigors of establishing an intracellular infection. Selected phenotypic variations in evading host defences have been correlated with expression of stage-specific proteins or functions. Resistance of trypomastigotes to complement-mediated killing correlates with the presence of a stage-specific molecule that exhibits an analogous function to mammalian decay-accelerating factor, and with the presence of a neuraminidase/trans-sialidase that transfers sialic acid moieties to the parasite surface, thereby enabling it to avoid complement activation. Trypomastigotes enter cells by a mechanism that involves sorting of cell surface receptors and avoids eliciting a respiratory burst. Once within a membrane-bound vacuole, which undergoes acidification, the neuraminidase/trans-sialidase and an acid-active, transmembrane pore-forming protein are released by the parasite and are capable of acting together to accelerate rupture of the vacuolar membrane and the parasite's escape into the cytoplasm of the host cell. Escape from the parasitophorous vacuole allows virulent stages of T. cruzi to avoid compartmental, non-oxidative killing mechanisms such as degradation by lysosomal hydrolases.


Subject(s)
Glycoproteins , Trypanosoma cruzi/pathogenicity , Animals , Humans , Models, Biological , Neuraminidase/metabolism , Protozoan Proteins/metabolism , Trypanosoma cruzi/growth & development , Trypanosoma cruzi/immunology , Virulence
10.
J Exp Med ; 176(2): 313-25, 1992 Aug 01.
Article in English | MEDLINE | ID: mdl-1500849

ABSTRACT

Trypanosoma cruzi enters host cells via formation of an acidic vacuole which is subsequently disrupted, allowing the parasite access to the cytoplasm. We show that in an acid environment, release of the parasite surface neuraminidase is enhanced, and this release is likely mediated by a phosphatidylinositol-specific phospholipase C (PIPLC), since antibodies to a carbohydrate epitope (CRD) revealed in glycosylphosphatidylinositol (GPI)-anchored proteins after PIPLC cleavage remove the great majority of the soluble neuraminidase activity from culture supernatants. The neuraminidase is active at acidic pH, and is capable of desialylating known vacuolar constituents, i.e., lysosomal membrane glycoproteins. Parasite escape into the cytoplasm is significantly facilitated in terminal sialylation-defective mutant Lec 2 cells, and enzymatically desialylated membranes are more susceptible to lysis by a parasite hemolysin previously implicated in vacuole membrane rupture. These findings provide evidence that terminal sialylation on carbohydrate moieties contributes to maintaining lysosomal membrane integrity, and indicate a role for a protozoan-derived neuraminidase in facilitating parasite entry into host cells. These observations raise the possibility that other microbial neuraminidases may serve a similar function in acidic intracellular compartments.


Subject(s)
Antigens, CD , Lysosomes/metabolism , Membrane Glycoproteins/metabolism , Neuraminidase/metabolism , Sialic Acids/metabolism , Trypanosoma cruzi/enzymology , Animals , CHO Cells , Cell Line , Cricetinae , Cytoplasm/parasitology , Fluorescent Antibody Technique , Hydrogen-Ion Concentration , Lysosomal Membrane Proteins , Lysosomes/ultrastructure , Microscopy, Electron , N-Acetylneuraminic Acid , Substrate Specificity , Trypanosoma cruzi/pathogenicity
11.
J Immunol ; 147(12): 4313-21, 1991 Dec 15.
Article in English | MEDLINE | ID: mdl-1753102

ABSTRACT

Trypanosoma cruzi, an obligate intracellular protozoan parasite, exhibits developmental regulation of virulence. Although both noninfective epimastigote and infective trypomastigote stages of T. cruzi enter phagocytic cells via the formation of a parasitophorous vacuole (PV), only the latter developmental stages survive ingestion and perpetuate the infection. To determine whether the membrane composition of PV surrounding these different stages might contribute to differences in the outcome of infection, we identified selected membrane constituents by immunofluorescence and intracellular radioiodination, and studied their incorporation into PV. Complement receptors (CR3) are incorporated preferentially into the PV membrane surrounding serum-opsonized epimastigotes but not culture-derived metacyclic trypomastigotes. FcR are not preferentially incorporated into PV membranes unless epimastigotes or culture-derived metacyclic trypomastigotes are opsonized with anti-T. cruzi antibody. PV surrounding either parasite stage contain beta 1 integrins and lysosomal membrane glycoproteins (lgp). These results indicate that the plasma membrane glycoproteins incorporated into the surrounding PV membrane differ depending upon the stage of parasite being internalized, and that these differences reflect, at least in part, selective ligation of cell surface receptors mediating uptake. Furthermore, they imply that although virulent trypomastigote stages may avoid host cell uptake by conventional phagocytic receptors, i.e., CR3 or FcR, they do not escape fusion with an lgp-containing vacuole where they could still be exposed to lysosomal antimicrobial mechanisms.


Subject(s)
Chagas Disease/metabolism , Macrophage-1 Antigen/analysis , Membrane Glycoproteins/analysis , Vacuoles/chemistry , Animals , Cells, Cultured , Fluorescent Antibody Technique , Integrins/analysis , Lysosomes/chemistry , Mice , Receptors, Fc/analysis
12.
AIDS Res Hum Retroviruses ; 7(8): 671-9, 1991 Aug.
Article in English | MEDLINE | ID: mdl-1931235

ABSTRACT

We have investigated the effects of human immunodeficiency virus type-1 (HIV-1) infection on constitutive and lipopolysaccharide (LPS)-induced expression of interleukin-6 (IL-6) in cultured blood monocyte-derived macrophages. Highly productive and cytopathic infection of macrophages was established with the macrophage-tropic HIV-1 BaL strain. On Days 14-28 post infection, infected and mock-infected cells were activated with LPS or control medium for 6-24 hours before harvesting culture supernatants and cellular RNA. IL-6 bioactivity in culture supernatants was measured with the IL-6-dependent B9 cell line. IL-6 mRNA levels were quantitated by Northern blot analysis with scanning densitometry. In the absence of LPS activation, IL-6 activity was near or below the limit of detection in supernatants from both infected and uninfected cultures. Similarly, without LPS stimulation, IL-6 mRNA was not detectable in either infected or uninfected macrophages. After activation with LPS, marked increases in IL-6 mRNA levels and supernatant bioactivity were evident in both infected and uninfected cultures, but the response to LPS was consistently greater in infected macrophages. LPS-induced IL-6 mRNA levels and supernatant bioactivity were 7.4- and 4.4-fold higher, respectively, in infected compared with uninfected macrophages (n = 5, p less than .05). These studies demonstrate that highly productive HIV-1 infection does not increase constitutive IL-6 expression in macrophages, but does prime macrophages for an augmented IL-6 response to LPS. These findings may help define the mechanisms responsible for increased IL-6 production in patients with HIV-1 infection.


Subject(s)
HIV-1/physiology , Interleukin-6/biosynthesis , Macrophages/microbiology , Cells, Cultured , Giant Cells , Humans , Kinetics , Lipopolysaccharides , Macrophages/immunology , Neutralization Tests , RNA, Messenger/metabolism , Virus Replication
13.
Immunol Today ; 12(3): A22-7, 1991 Mar.
Article in English | MEDLINE | ID: mdl-2069674

ABSTRACT

During the course of establishing infection in a susceptible host, obligate intracellular parasites evade host defence mechanisms before, during and after entry into host cells. Before entry they circumvent the lytic activity of the complement cascade, during cell entry they avoid being killed by toxic oxygen metabolites and after entry they escape nonoxidative killing mechanisms such as degradation by lysosomal hydrolases. Different intracellular parasites, exemplified here by Leishmania spp, Trypanosoma cruzi and Toxoplasma gondii, undermine host defences at each step by various strategies that ultimately ensure their targeting to, and survival in, an appropriate intracellular compartment.


Subject(s)
Adaptation, Biological , Host-Parasite Interactions , Parasitic Diseases/physiopathology , Phagocytes/parasitology , Animals , Cell Compartmentation , Complement Activation , Free Radicals , Leishmania/physiology , Lysosomes/enzymology , Oxygen/metabolism , Receptors, Complement/physiology , Toxoplasma/physiology , Trypanosoma cruzi/physiology , Vacuoles/parasitology
14.
J Immunol ; 144(7): 2751-6, 1990 Apr 01.
Article in English | MEDLINE | ID: mdl-1690776

ABSTRACT

Schistosoma mansoni parasites recovered from the blood stream were found to be nonactivators of the alternative complement pathway (ACP) when exposed to sera of homologous but not heterologous host species. Schistosomes could be converted into activators of the homologous ACP by treatment with phospholipase C. Antibodies to either human or guinea pig decay accelerating factor (DAF), a 70-kDa glycosylphosphatidylinositol anchored membrane glycoprotein which controls ACP activation on the mammalian cell plasma membrane, bound to the surface of immature schistosomes and immunoprecipitated a molecule of similar molecular mass from detergent extracts of surface iodinated parasites. Phospholipase C treatment drastically reduced the reactivity of the worms with the anti-DAF antibodies. These data suggest that schistosomes evade the ACP by inserting functional host DAF into their surfaces, possibly through adsorption of the molecule's lipophilic diacyglycerol membrane anchor moiety into the outer lipid bilayer of the parasite.


Subject(s)
Complement Activation , Complement Inactivator Proteins/physiology , Complement Pathway, Alternative , Membrane Proteins/physiology , Schistosoma mansoni/immunology , Type C Phospholipases/pharmacology , Adsorption , Animals , CD55 Antigens , Cell Membrane/physiology , Fluorescent Antibody Technique , Guinea Pigs , Macaca mulatta , Mice , Rabbits
15.
J Immunol ; 143(2): 617-22, 1989 Jul 15.
Article in English | MEDLINE | ID: mdl-2525590

ABSTRACT

The role of complement receptors on monocyte derived human macrophages in phagocytosis of infective (MP) and noninfective (LP) developmental stages of Leishmania major promastigotes was studied. We compared binding of these specific developmental stages to MO after preincubation in fresh or heat-inactivated serum. Although LP do not require fresh serum for attachment, MP were dependent on serum C opsonization for entry. Inhibition of CR1 substantially abolished binding of the infective MP. In contrast, inhibition of iC3bR (CR3 and p150,95) had no effect on MP binding. Inhibition of both iC3bR, however, did block binding of nonopsonized LP. Attachment of LP to CR3 was blocked by fluid phase addition of mAb OKM1 and M1/70, which inhibit complement-independent binding to CR3, but not by mAb OKM10 which inhibits iC3b binding to this receptor. After fresh serum pretreatment of LP, however, only simultaneous inhibition of CR3 and CR1 effectively blocked their attachment. Addition of mannan did not inhibit attachment of either promastigote stage. Both opsonized and nonopsonized LP trigger a respiratory burst in MO, possibly via the C independent site in CR3, whereas the CR1-mediated uptake of MP does not generate a respiratory burst. The use of this receptor by MP may facilitate their subsequent intracellular survival.


Subject(s)
Cell Adhesion , Complement C3b/metabolism , Leishmania tropica/physiology , Leishmaniasis/metabolism , Macrophages/immunology , Receptors, Complement/physiology , Animals , Binding, Competitive , Blood Physiological Phenomena , Cell Adhesion/drug effects , Humans , Leishmania tropica/growth & development , Leishmaniasis/immunology , Leishmaniasis/parasitology , Macrophages/parasitology , Mannans/pharmacology , Receptors, Complement/drug effects , Receptors, Complement 3b
18.
J Exp Med ; 148(1): 46-57, 1978 Jul 01.
Article in English | MEDLINE | ID: mdl-97360

ABSTRACT

Schistosoma mansoni schistosomula recovered from the lungs of inbred mice were shown to possess serologically detectable alloantigens on their tegumental surfaces. Using appropriate antisera and infected congenic and recombinant mice as worm donors, gene products of the K and I subregions of the major histocompatibility complex were demonstrated among these alloantigens acquired by the parasites. In contrast, other cell surface alloantigens, such as Thy 1, Ly 1, and H-Y and the serum proteins albumin, C3 and Ig, could not be detected on the surface of lung schistosomula by means of comparable techniques. In another series of experiments, schistosomula recovered from the lungs of mice and reinjected into allogeneic recipients were shown to exchange their alloantigens during an 87-h period of examination. Similarly, lung schistosomula cocultured with allogeneic lymphocytes were shown to acquire major histocompatibility complex (MHC) coded antigens from the cells. It is possible that as acquired host molecules, MHC gene products may disguise the surface of schistosome parasites thereby rendering them insusceptible to immune attack.


Subject(s)
Genes, MHC Class II , Histocompatibility Antigens , Mice, Inbred Strains/parasitology , Schistosoma mansoni/immunology , Animals , Disease Models, Animal , Female , Fluorescent Antibody Technique , Lung/parasitology , Male , Mice , Mice, Inbred Strains/immunology , Protein Biosynthesis , Schistosomiasis/genetics , Schistosomiasis/immunology
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