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H Drobecq

Publications and source records attributed to H Drobecq.

24 records · Page 2Linked to original sources

Synthetic peptides approach to identification of epitopes on bovine leukemia virus envelope glycoprotein gp51.

Peptides corresponding to residues 21-28, 39-48, 57-67, 59-69, 78-92, 144-155, 144-157, 195-205, 255-268, and 260-268 of envelope glycoprotein gp51 of bovine leukemia virus (BLV) were chemically synthesized and coupled to keyhole limpet hemocyanin or tetanus toxoid. All peptides were immunogenic in rabbits and induced production of antipeptide antibodies. Enzyme-linked immunosorbent assays using Tween 80-purified gp51 or BLV particles showed that antibodies against peptides 78-92, 255-268, and to a lesser extent 39-48 and 144-157 were able to react with the parent glycoprotein, purified or as an integer part of BLV particles. Antisera against peptides 39-48, 78-92, and 144-157 neutralized VSV (BLV) pseudotypes in vitro, the highest neutralization titer being obtained with the 78-92 cyclized peptide. These observations confirm that the NH2 moiety of gp51 carries epitopes involved in virus infectivity.

Animals↗

Analysis of T and B cell epitopes of the Schistosoma mansoni P28 antigen in the rat model by using synthetic peptides.

The Schistosoma mansoni P28 molecule is an Ag inducing protective immunity in various experimental models. Three synthetic peptides, derived from the primary sequence of the recombinant P28 and comprising amino acids 24-43, 115-131, and 140-153, respectively, were synthesized according to their hydrophilicity, mobility, and accessibility profiles. The presence of B and T lymphocyte epitopes in these peptides has been examined in the rat model. The results showed that the 24-43 and the 115-131 peptides contained major epitopes for IgG but not for IgE. Moreover, the 24-43 peptide-specific IgG produced after injecting either the recombinant P28 Ag or the 24-43 peptide coupled to tetanus toxoid was essentially of the IgG2a subclass and to a lesser extent of the IgG1 subclass, whereas no IgG2c was detected. These 24-43 peptide-specific antibodies were cytotoxic in vitro for schistosomula in the presence of eosinophils as effector cells. The 24-43 and the 140-153 peptides contained major targets of T lymphocytes specific for the recombinant P28 Ag. T cell lines specific for the 24-43 peptide have been prepared. These cells proliferated in vitro when stimulated with various S. mansoni crude antigenic preparations or with the recombinant P28 Ag. Moreover, their passive transfer to rats immunized with the P28 Ag led to a significant increase in specific IgE without modifying the IgG response.

Animals↗

Influence of helical organization on immunogenicity and antigenicity of synthetic peptides.

Using cooperative effects of different peptide structures synthesized in tandem, we have induced an alpha-helical structure in water solution on a peptide which, alone, is unorganized. This structure is particularly relevant in this case as the selected model protein (type 24 M protein of Streptococcus pyogenes) is an extended coiled-coil system. We were thus able to assess the importance of organization or unorganization of a unique amino acid sequence with regards to its immunogenicity and antigenicity. Although in a classical manner, antibodies cross-reacting with the protein can be obtained with the short, unorganized peptide, we demonstrate that conformation-specific antibodies are raised when longer, organized peptides are used as immunogens.

Animals↗

Fluorescence-activated cell-sorting analysis of fibronectin peptides binding to Trypanosoma cruzi trypomastigotes.

The binding of synthetic peptides modeled from the sequence of the cell attachment site of fibronectin to T. cruzi trypomastigote surface receptors was investigated by fluorescence-activated cell-sorting analysis using fluorescein-labeled peptides. Peptides with the sequence Arg-Gly-Asp-Ser bound to the parasite surface. A low percentage of fresh parasites recently liberated from infected fibroblasts had the capacity to bind the peptide. In contrast, these parasites showed a time-dependent several-fold increase in their ability to bind the Arg-Gly-Asp-Ser-containing peptides during extracellular incubation. From these observations, it appears that the expression of surface receptors on a particular, mature stage of the parasite parallels its ability to adhere to and infect host cells.

Amino Acid Sequence↗

Structural requirements for the induction of "immunological castration" by linear monomeric LHRH-lys-MDP administered in saline.

It was previously shown that "castration" could be obtained in male mice by immunizing them in saline with a conjugate referred to as LHRH-Lys-MDP and containing the decapeptide hypothalamic hormone LHRH covalently linked to the adjuvant glycopeptide MDP-Lys. Since coupling was made using carbodiimide, it could have produced oligomers or isomers as well as monomers. In the present investigation male and female mice were immunized in saline with a linear monomeric MDP linked LHRH molecule obtained by total synthesis. Histological studies showed gonadal alterations in both male and female mice. The study of analogs provided a correlation between the "castrative" activity of LHRH-Lys-MDP and its chemical and antigenic structures. However, because LHRH antibody levels were not very high, mechanisms other than antibody response are discussed. Such totally synthesized molecules including a safe adjuvant could make a clinical use of LHRH immunization possible in endocrine-dependent cancers.

Acetylmuramyl-Alanyl-Isoglutamine↗

Synthesis of conjugates between luteinizing hormone releasing hormone (LH-RH) and N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP) models of totally synthetic vaccines.

Two glycopeptides associating the aminoacid sequence of LH-RH with MDP were prepared, using a Lys residue as a linker. These conjugates, N alpha MDP N epsilon (LH-RH)-Lys and N alpha MDP N epsilon (LH-RH)-Lys-NH2 obtained by condensation of fragments were synthesized by liquid as well as solid phase methods. Both compounds were able to induce anti LH-RH antibodies and immunological castration. They retained the immuno-adjuvant activity of MDP. Such antigen-adjuvant constructs, devoid of carrier and obtained by chemically defined and reproducible synthetic methods could offer suitable tools for structure-activity relationship studies aiming at defining synthetic vaccines.

Acetylmuramyl-Alanyl-Isoglutamine↗