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Biomedical subjects

A Capron

Publications and source records attributed to A Capron.

At least 37 records · Page 2Linked to original sources
PubMed1992

Eosinophil IgE receptor and CD23.

In the present review, eosinophil Fc epsilon RII was compared to CD23, a differentiation marker of B cells. Biochemical analysis revealed that molecules of similar molecular weight were immunoprecipitated from eosinophils and B cells by an anti-CD23 monoclonal antibody (mAb) or by BB10, and anti-eosinophil Fc epsilon RII. By flow cytometry, a correlation was found between the binding of anti-CD23 mAb and myeloma IgE. However, a low expression of different epitopes of CD23 was observed in various hypereosinophilic patients. Northern blot analysis of eosinophil RNA with the cDNA probe of CD23 revealed a weak message in only 3 of the 6 patients expressing membrane CD23. The inhibition by anti-CD23 mAbs of IgE-mediated cytotoxicity and IgE binding to eosinophils clearly indicated the participation of CD23 or a related molecule in IgE-dependent eosinophil functions. However, the differential effects of anti-CD23 mAbs on eosinophils and B cells suggest major differences in the characteristics of the molecule expressed by eosinophils and by B cells.

Antibodies, Monoclonal↗
PubMed1992

TNF-alpha production by U937 promonocytes is enhanced by factors released from HIV-infected T4 lymphocytes: TNF-alpha is one of the mediators causing lysis of HIV-infected T4 cells.

In the present study, we have shown that the addition of culture supernatants from HIV-infected SupT1 cells (T4) but not from noninfected cells markedly increased the production of TNF-alpha by U937 promonocytic cells after stimulation with phorbol 12-myristate 13-acetate (PMA). Pretreatment of supernatants with the antibodies to granulocyte/macrophage colony-stimulating factor (GM-CSF) or TNF-alpha, but not interferon-gamma, significantly diminished this enhancing effect. These results suggest that HIV may play an indirect role by producing cytokines from infected T4 cells that can lead to an increased production of TNF-alpha by monocytic cells. Further, TNF-alpha produced by U937 cells following stimulation with PMA plus lipopolysaccharide or with phytohemagglutinin induced lysis of HIV-infected T cells. TNF-alpha-induced cytotoxicity was markedly higher toward HIV-infected than toward noninfected T4 cells. Addition of antibody to TNF-alpha during the cytotoxic phase of response resulted in a reduction of about 50% in the percentage of cytotoxicity, indicating TNF-alpha as one of the lytic mediators.

Antibodies↗
PubMed1992

T helper cell epitopes of the human immunodeficiency virus (HIV-1) nef protein in rats and chimpanzees.

T helper cell antigenic and immunogenic determinants of the nef protein were investigated in the rat and chimpanzee models using recombinant nef protein and five synthetic peptides selected according to their amphipathic and alpha-helicity properties. The nef protein was shown to be immunogenic with both Freund's or aluminium hydroxide adjuvants. After immunization with the nef protein the 45-69 peptide was the most antigenic in rat and monkey models. In contrast, the 98-112 peptide, that required a carrier protein to induce in vitro rat T cell recall proliferation, was able to restimulate monkey T cells in the absence of a carrier. The amino acid sequence carrying the antigenic activity of the 45-69 peptide was further investigated by synthesizing short peptides overlapping this region. The antigenic sequence was precisely located in the middle of the peptide (region 50-59). This sequence was antigenic only when N alpha-acetylated. Circular dichroism analysis of the 45-69 peptide and the in vitro activity of the N-terminus group indicate in this case the involvement of the alpha-helical propensity for antigen presentation. However, the shorter sequence 50-64, able to induce a T cell reactivity, was determined as a beta-pleated sheet structure in aqueous solution. The 45-69 peptide was not only antigenic but also immunogenic and behaved in vivo as a functional T helper cell epitope. Indeed, the priming with the peptide or the transfer of peptide specific T cells to a naive recipient, followed by immunization with the nef protein, enhanced the subsequent antibody response to the nef protein. Together, these data indicate that the 45-69 peptide appears as a candidate for the in vivo elicitation of T cell immunity to the HIV-1 nef regulatory protein.

Amino Acid Sequence↗
PubMed1992

Determination of B-cell epitopes of nef HIV-I protein: immunogenicity related to their structure.

Determination of the B-cell epitopes of the nef molecule encoded by the human immunodeficiency virus type 1 (HIV-1) was undertaken using a set of six synthetic peptides. Sequences that were both antigenic and immunogenic and stimulated the production of antibodies recognizing the full length molecule, were considered as B-cell epitopes. Two peptidic sequences were antigenic both in rodents (mice and rats) and in non-human primates (chimpanzee). They were located in the regions 45-69 and 176-206 of the nef molecule. Two additional antigenic sequences were determined, one in chimpanzees, region 79-94, and the second in rodents, region 148-161. Immunogenicity was investigated in the rodents. Only the 45-69 and 176-206 sequences were immunogenic, and specific antibodies present in the sera of the immunized animals reacted with the nef protein. Therefore, each of these two sequences could be considered as containing at least one B-cell epitope. The fine epitopic specificity was determined using subfragments of these two sequences and it was shown that the antigenic determinants were contained in the C-terminal region of each sequence overlapping with the T-cell epitopes. These results raised the importance of vicinity of B- and T-cell determinants and their immunogenicity.

Amino Acid Sequence↗
PubMed1992

Amino acid sequence requirements for the epitope recognized by a monoclonal antibody reacting with the secreted antigen GP28.5 of Toxoplasma gondii.

We have characterized in detail, the epitope of the secreted antigen GP28.5 recognized by the mouse monoclonal antibody TG 17-179 using synthetic peptides and a truncated recombinant fusion protein. The screening of a T. gondii expression library with TG17-179 mAb led to the isolation of cDNAs clones, all encoding for the C-terminal region of GP28.5 and with one encoding for only the five last C-terminal residues. Competitive ELISA with longer peptides revealed that the immunoreactivity was retained for peptides of eight residues or longer, and lost when the peptide was reduced to the six last C-terminal residues or less. Experiments with the octapeptide lacking the carboxy-terminal glutamine residue showed it to be 64-fold less active. Moreover, neither addition of residues in the carboxy-end nor substitution of COOH function changed the immunoreactivity of the epitope. Competition experiments between TG17-179 mAb and sera from infected individuals demonstrates that the epitope defined by a mouse monoclonal probe is also a major epitope for human polyclonal antibodies. These results describe the sequence requirements within a probably linear epitope and give rise to some general question concerning experimental test for epitope mapping.

Amino Acid Sequence↗
PubMed1992

Analysis of antigenicity and immunogenicity of five different chemically defined constructs of a peptide.

The aim of this study was to compare the antigenicity and the immunogenicity of five constructs of a peptide, including the peptide in single copy, a tandem repeat containing three copies, a copolymer with glutaraldehyde and two constructs based on the MAP (Multiple Antigenic Peptide) model, one containing two copies (MAP-2) and the other, eight copies of the peptide (MAP-8). The peptide used in this test was the 115-131 sequence derived from the rSm28-GST antigen of Schistosoma mansoni. All constructs were recognized by rSm28-GST specific antibodies in solid phase immunoassays. However, the binding was higher when the MAP-8 was used as antigen at least partly because of its better coating on the microtiter plates. In vitro lymphoproliferative assays showed that polymer was mitogenic, repeat and MAP-2 did not stimulate rSm28-GST specific T cells while MAP-8 induced a slight response. The injection of MAP-8 to rats led to important antibody and T cell responses higher than those obtained with the other constructs. The IgG2a (cytotoxic antibody in schistosomiasis)/IgG2c (blocking antibody) ratio was independent of the immunogen. Taken together these results demonstrate that both the antigenicity and the immunogenicity of a peptide containing T and B cell epitope(s) are strongly related to the molecular form whereby it is presented and that the MAP-8 construct can be useful in serodiagnosis or in vaccination trials using synthetic peptides.

Amino Acid Sequence↗
PubMed1992

Inter-species variation of schistosome 28-kDa glutathione S-transferases.

The 28-kDa glutathione S-transferase from Schistosoma mansoni (Sm28GST) is a candidate vaccine antigen. To evaluate the antigenic and phylogenetic variations between the 28-kDa GSTs from 4 species of schistosome, we have cloned and sequenced the 28-kDa GSTs from Schistosoma haematobium (Sh28GST) and Schistosoma bovis (Sb28GST). Sb28GST and Sh28GST are more similar to each other (97%) than to Sm28GST (90%) and particularly to the 28-kDa GST from Schistosoma japonicum (Sj28GST, 77%). Antisera directed against the major Sm28GST epitopes revealed differences in the recognition of the 28-kDa GSTs from the other schistosome species suggesting that these regions have been subjected to evolutionary pressure. The consequences of such species-specific epitopes on the development of a multi-species anti-schistosome vaccine are discussed.

Amino Acid Sequence↗
PubMed1992

Cloning and sequencing of a 24-kDa Trypanosoma cruzi specific antigen released in association with membrane vesicles and defined by a monoclonal antibody.

In the present study we have used the Tcr7 monoclonal antibody (mAb) previously characterized as directed against Trypanosoma cruzi 24-25-kDa specific antigens, both are immunogenic in man and during experimental T cruzi infections. We have demonstrated that mAb Tcr7 was able to recognize two in vitro translation products of molecular weights of 24 and 25 kDa. This suggested the holoproteic nature of these two related antigens bearing at least a common epitope and allowed us to use Tcr7 for an immunoscreening of a lambda ZAPII T cruzi cDNA library. Indeed, we have obtained several positive clones and completely sequenced the largest one which encoded theoretically for a protein of 23.7 kDa. The sequence analysis revealed a nearly perfect homology between this clone and one already described by other investigators and was shown to express a major flagellar protein of T cruzi able to bind calcium. Using different overlapping peptides derived from the sequence of the cDNA clone, we have localized the immunoreactivity of mAb Tcr7 mainly on several primary sequences present in the N-terminal part of the sequence, suggesting that the mAb could recognize a discontinuous epitope. Moreover, the immunoelectron microscopy allowed us to show that the antigen(s) carrying the epitope reacting with mAb Tcr7 is (are) released in association with membrane vesicles which protruded from the parasite surface and the flagellar pocket. This new mechanism of antigen shedding is likely to be independent of phospholipase C-mediated release of GPI-anchored molecules.

Amino Acid Sequence↗
PubMed1992

Trypanosoma cruzi glutathione-binding proteins: immunogenicity during human and experimental Chagas' disease.

Following purification by affinity chromatography, three glutathione-binding proteins (TcGBP) of 45, 30, and 25 kDa were co-purified from Trypanosoma cruzi epimastigotes. Using 1-chloro-2,4 dinitrobenzene as substrate, a glutathione S-transferase activity of 70 nmol/min/mg of proteins was detected in the GSH binding fraction. An increased expression of TcGBP and total GST activity was observed upon incubation of parasites with phenobarbital, which is an inducer of GST synthesis. Immunofluorescence and electron microscopic experiments demonstrated that TcGBP were expressed by all developmental stages of the parasite, including infective forms. The expression of these proteins by intracellular dividing amastigotes could be in favour of a potential defensive role of these molecules against host attack. Results obtained by immunoprecipitation of in vitro translation products using anti-TcGBP antisera suggested that these three polypeptides are not glycosylated. In addition, antibodies directed against the TcGBP were found in a high proportion of T. cruzi-infected chronic chagasic patients' sera and in sera of chronically infected BALB/c mice. In contrast, acute chagasic patients' sera and acute-phase mouse sera were found to be poorly reactive with these proteins. Our results identify a new class of potential target antigens, which may be essential for the development of T. cruzi in its host. Their protective role in experimental models deserves to be investigated.

Animals↗
PubMed1992

Levels of soluble IL-2 receptor in plasma from asthmatics. Correlations with blood eosinophilia, lung function, and corticosteroid therapy.

Evidence now suggests that eosinophils and T lymphocytes infiltrating bronchial tissues may play a key role in the pathophysiology of asthma. Circulating eosinophils, lung function, and plasma soluble IL-2 receptor (sIL-2R) were measured in 42 asthmatic patients referred for symptomatic asthma. The patients were divided into two groups based on the presence or absence of atopy. The group of non-atopic asthmatics was further divided according to the patients' requirement for long term oral corticosteroids. The mean sIL-2R +/- s.d. was 36.3 +/- 9.9 pM in the control group, 28.9 +/- 9.2 pM in the atopic asthmatics, 43.3 +/- 18.07 pM in the non-atopic asthmatics without oral steroid therapy, but was increased in the steroid-treated group (62.2 +/- 19.3 pM, P less than 0.01). A significant correlation was found between FEV1 and circulating eosinophils in atopic asthmatics and in non-atopic asthmatics without oral corticosteroid therapy, but not in the steroid-treated group. Furthermore, significant correlations were found between sIL-2R and FEV1, and between sIL-2R and blood eosinophils, in the group of non-atopic asthmatics not on oral steroid therapy. No such correlations were evidenced in the other groups of asthmatics. Similar results were obtained during the clinical course of three non-atopic patients followed for more than 1 year. These data suggest that T cell activation appears more prominent in non-atopic asthma than in atopic asthma. Moreover, it appears that T cell activation can occur in severe forms of asthma despite steroid treatment. Finally, the results suggest a possible link between T cell activation, eosinophils, and lung function, which may reflect a particular pathogenetic mechanism involved in non-atopic asthma.

Adrenal Cortex Hormones↗
PubMed1992

T-cell-dependent immunity and thrombocytopenia in rats infected with Plasmodium chabaudi.

Normal, splenectomized, and athymic Fischer rats were infected with Plasmodium chabaudi. In normal rat infections, acute-phase infection resolved rapidly and completely. In splenectomized rats, infection resulted in high parasitemia and ultimately death. In nude rats, parasite growth was reduced compared with normal rats, and a persistent parasitemia (between 20 and 45%) was observed for several months. Complete resolution of the infection was achieved after adoptive transfer of T lymphocytes, even when transfer occurred during the course of infection. These results indicated that an acquired, T-lymphocyte-dependent immunity was necessary for the complete recovery observed in normal rats. In normal rats, thrombocytopenia and splenomegaly occurred during infection. By contrast, in nude rats, both of these pathological manifestations were only observed after thymus grafting. Thrombocytopenia was also absent in the splenectomized animals. Despite an increase in platelet-associated immunoglobulin levels during the infection, thrombocytopenia was not transferred by injection of infected rat serum to normal recipients. It has been concluded that the nude rat infection can be regarded as a novel and useful model for studying the T-cell-dependent effector and pathological mechanisms and to investigate the anti-P. chabaudi immune response.

Animals↗
PubMed1992

Polyclonal cell activity of a repeat peptide derived from the sequence of an 85-kilodalton surface protein of Trypanosoma cruzi trypomastigotes.

Some in vitro and in vivo biological activities of an octadecapeptide derived from an 85-kDa surface protein of Trypanosoma cruzi trypomastigote were studied. The peptide coupled to a carrier protein induced the proliferative response of lymph node cells from mice immunized with various antigens. Moreover, sera from mice immunized with the coupled peptide were found to contain antibodies against a number of self and nonself antigens: fibronectin, bovine serum albumin, myosin, tetanus toxoid, ovalbumin, keyhole limpet hemocyanin, and DNA. These results are discussed in the context of Chagas' disease immunopathology.

Amino Acid Sequence↗
PubMed1992

Immunologic aspects of schistosomiasis.

Immunity to schistosomes, helminth worms that infect 200 million people, is targeted to invading larvae (concomitant immunity). In vitro studies have revealed the role of T cells and of particular antibody isotypes in immune defense: IgE antibody cooperates with mononuclear phagocytes, eosinophils, and platelets to kill schistosome larvae. IgE antibody appears as an essential component of acquired resistance in rats. The role of IgE antibody has recently been confirmed by epidemiological studies demonstrating a positive correlation between the acquisition of resistance to reinfection by schistosomes and the level of IgE antibody to the parasite. A negative correlation found in these studies with the levels of IgM, IgG2, or IgG4 antibodies could be related to the development of a blocking antibody response. Antigens involved in protective immunity are expressed transiently at the surface of schistosomes. Sm28, a glutathione-S-transferase, induces significant protection against schistosome infection in rodents and nonhuman primates. In addition, this vaccine reduces the size of egg granulomas and egg output. Besides allowing the definition of a vaccine strategy against a major disease, studies on immunology of schistosomiasis have unraveled unsuspected antigenic mimicry between schistosomes and HIV regulatory proteins and have led to the demonstration that IgE antibody, a protective isotype against helminths, may also activate Fc epsilon-RII-bearing mononuclear phagocytes, eosinophils, and platelets in allergic disease.

Animals↗
PubMed1992

Specific activation of platelets from patients allergic to Dermatophagoides pteronyssinus by synthetic peptides derived from the allergen Der p I.

Previous studies have shown that Fc epsilon RII-bearing platelets from patients with allergic disorders could be stimulated either by anti-human IgE antibodies or the relevant allergens to generate cytotoxic mediators. In this report, the reactivity of platelets from Dermatophagoides pteronyssinus (D. pt)-sensitive patients to three Der p I-derived synthetic peptides (52-71, 117-133 and 188-199) was investigated. The platelet stimulation observed in D. pt-sensitive patients was demonstrated to be allergen-specific and to be mediated by IgE. These Der p I-derived peptides failed to stimulate platelets from healthy donors or platelets from non-D. pt-allergic patients. D. pt-sensitive patients responded more frequently to the peptides 52-71 and 117-133 than to the peptide 188-199. Thus, in this model, synthetic peptides selected for their assumed accessibility on the native antigen could be associated to an IgE-dependent biological activity.

Adult↗
PubMed1992

Tumor necrosis factor alpha and interleukin-6 production by human mononuclear phagocytes from allergic asthmatics after IgE-dependent stimulation.

We have previously demonstrated the production of tumor necrosis factor alpha (TNF) and interleukin-6 (IL-6) by alveolar macrophages (AM) from allergic asthmatics developing a late asthmatic reaction after bronchial allergen challenge. In order to explain the modalities of this monokine synthesis, we tested in vitro the effect of an IgE-dependent stimulation on blood monocytes (BM) and AM from control and asthmatic subjects. TNF and IL-6 secretions were evaluated in 24-h supernatants by radioimmunoassay and by the 7TD1 cell proliferation test, respectively. AM from allergic asthmatics secreted spontaneously higher concentrations of TNF and IL-6 than did BM or AM from control subjects. BM from asthmatics also produced spontaneously increased levels of TNF, but at a lesser degree than did AM. The addition of anti-IgE induced a significant increase of TNF and IL-6 secretions by mononuclear phagocytes from control subjects only after previous sensitization with IgE-rich medium. In contrast, the direct stimulation by allergen or anti-IgE of AM and BM from asthmatics enhanced significantly the production of TNF and IL-6 when compared with cells cultured in medium alone. In these conditions, IgE-dependent activation of cells from allergic asthmatics compared with those from control subjects increased monokine production in a similar manner. Costimulation by recombinant human interferon gamma and IgE-dependent triggering had a synergistic effect on TNF production, but it had only an additive action on IL-6 synthesis (respective increase index: 9.8 compared with 2.9 and 9.8 compared with 2.1, respectively, for BM from control and asthmatic subjects).(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗