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A Delmas

Publications and source records attributed to A Delmas.

At least 19 recordsLinked to original sources
PubMed1997

Structural properties of chimeric peptides containing a T-cell epitope linked to a fusion peptide and their importance for in vivo induction of cytotoxic T-cell responses.

We have previously shown that when administered to mice without adjuvant, a chimeric peptide consisting of the fusion peptide F from measles virus protein linked at the C-terminus of a cytotoxic T-cell epitope from the M2 protein of respiratory syncytial virus efficiently primes for an major histocompatibility complex (MHC) class-I restricted cytotoxic T lymphocyte (CTL) response. In this report, we demonstrated by microspectrofluorometry that the fusion-peptide moiety bound to the plasma membrane of living cells. When the fusion peptide was linked to the C-terminus of the CTL epitope, the chimeric peptide (M2-F) adopted a marked beta-sheet conformation. In contrast, when the fusion peptide was linked to the N-terminus of the T-cell epitope (F-M2), the chimeric peptide adopted an alpha-helical conformation in the presence of trifluoroethanol. The immunogenicity of the two chimeric peptides for class-I restricted CTL was also significantly different, the one adopting the alpha-helical conformation being more immunogenic. Probably due to its obvious conversion to an alpha-helical conformation, the F-M2 peptide could have a higher propensity to insert into membranes, as shown by microspectrofluorometry, with a resultant better immunogenicity than the M2-F peptide.

Amino Acid Sequence↗
PubMed1997

Fine specificity of the antibody response to a synthetic peptide from the fusion protein and protection against measles virus-induced encephalitis in a mouse model.

A synthetic peptide representing residues 397-420 from the measles virus (MV) fusion (F) protein was tested for its structure, immunogenicity and protective capacity against intracerebral challenge with a neuroadapted strain of MV. Analysis of the peptide by mass spectrometry showed that it was linear, despite the presence of two cysteine residues in the sequence. Circular dichroism spectroscopy highlighted a weak preference for the peptide to adopt an alpha-helical conformation. The peptide was shown to be immunogenic in BALB/c and C57BL/6 mice after intraperitoneal immunization in Freund's adjuvant, and anti-peptide antibodies from both strains of mice reacted with the MV as a solid phase antigen on an ELISA plate. When the fine specificity of the anti-peptide antibody response was examined using overlapping 8-mer peptides, serum antibodies from BALB/c mice recognized the region between residues 407-417 whereas antibodies from C57BL/6 mice recognized the region 408-420 of the 397-420 peptide sequence. Although anti-397-420 antibodies had no demonstrable neutralizing activity, protection against challenge with a neuroadapted strain of MV was demonstrated following active immunization with peptide in C57BL/6 mice or after passive transfer of anti-peptide antibodies in BALB/c mice. These findings highlight the importance of the 397-420 region in the induction of protective antibodies in the MV encephalitis mouse model, and suggest that this epitope might be a good candidate for inclusion in a future MV synthetic peptide vaccine.

Animals↗
PubMed1996

Efficient binding to the MHC class I K(d) molecule of synthetic peptides in which the anchoring position 2 does not fit the consensus motif.

Peptides eluted from the MHC class I K(d) molecule are generally nonamers that display a strong preference for Tyr in position 2 and Ile or Leu in position 9. We investigated the binding ability of several synthetic peptides which did not fit this consensus motif. In our peptides, Tyr(2) was substituted by other amino acids, i.e. LeU, Ile or Met. These peptides were variants of the 252-260 K(d)-restricted peptide SYIPSAEKI derived from the Plasmodium berghei circumsporozoite protein. They bound to purified K(d) molecules in vitro with intermediate affinity. One of them was tested for in vivo stimulation of T cells and induced a cytotoxic response. These results demonstrate the importance of binding motif refinement to discover new binding characteristics and new ligands such as low-affinity peptides.

Amino Acid Sequence↗
PubMed1996

The binding of chimeric peptides to GM1 ganglioside enables induction of antibody responses after intranasal immunization.

With a model peptide, the neutralizing epitope 50-75 of cholera toxin B subunit, two chimeric peptides were constructed. A T-cell epitope, the 174-187 peptide from the G protein of the respiratory syncytial virus, was co-linearly synthesized at the amino-(174-50) or carboxyl-terminus (50-174) of the 50-75 peptide. Although both chimeric peptides were equally immunogenic by the intraperitoneal route, the 50-174 peptide was more immunogenic than the 174-50 peptide by the intranasal (i.n.) route. Both chimeric peptides inhibited the binding of cholera toxin B subunit to GM1 ganglioside with the 50-174 peptide being more effective inhibitor than the 174-50 peptide. In addition, an effective priming of the immune system was achieved after the i.n. administration of immunogens. The observed unresponsiveness after the i.n. co-immunization with the 50-174 peptide and GM1 ganglioside emphasize the role of GM1 binding for the induction of an immune response after i.n. immunization.

Administration, Intranasal↗
PubMed1996

Linkage of a fusion peptide to a CTL epitope from the nucleoprotein of measles virus enables incorporation into ISCOMs and induction of CTL responses following intranasal immunization.

The introduction of soluble protein antigens into the endogenous processing pathway is a prerequisite for the efficient induction of MHC class-1 restricted cytotoxic T-lymphocytes (CTLs). Antigens incorporated into immunostimulating complexes (ISCOMs) containing lipids and Quil-A are able to induce CD8+ CTL responses in vivo. Furthermore, lipopeptides have also been used to raise peptide-specific CTLs and bypass the requirement for the use of an adjuvant. Although conventional ISCOM technology is in general restricted to the use of hydrophobic proteins or fatty acid-derivitized proteins or peptides, we have demonstrated that the linkage of a conserved paramyxovirus fusion peptide to a CTL epitope NP29 (residues 281-290 of measles virus nucleoprotein) resulted in the incorporation of this hydrophilic CTL epitope into ISCOMs and the in vivo priming of peptide specific CTLs following intranasal immunization. In addition, the fusion peptide-CTL epitope chimera was able to efficiently sensitise P815 target cells for lysis by nucleoprotein specific CTLs induced following immunization of mice with recombinant RAd-68 adenovirus, suggesting the efficient introduction of the peptide into the class-1 restricted antigen processing pathway. Furthermore, immunization of mice with this fusion peptide chimera in saline was able to prime an NP29-specific CTL response despite the absence of adjuvant.

3T3 Cells↗
PubMed1996

Structural requirements for synthetic immunogens to induce measles virus specific CTL responses.

We have studied the immunogenicity of a synthetic peptide representing a cytotoxic T cell epitope (CTL) from the nucleoprotein of measles virus (MV). For the induction of peptide and MV-specific CTL responses after subcutaneous immunization, covalent linkage of the CTL epitope to a T-helper epitope was required. The presence of two copies of the T-helper epitope at the amino terminus of the CTL epitope (TT-CTL) resulted in the induction of strong CTL responses after administration in saline. In contrast, a chimeric peptide with one copy of the T-helper epitope at the amino terminus of the CTL epitope (T-CTL) was weakly immunogenic when given in saline. Analysis of the structure of the TT-CTL chimeric peptide by CD spectroscopy revealed an alpha-helical conformation, as compared to the random coil conformation favored by the T-CTL chimeric peptide. In addition, the CD spectra of the TT-CTL peptide in the presence of small unilamellar vesicules (SUV) revealed an increased helicity, as compared to the spectra of the T-CTL chimera in the presence of SUV. This suggests that the amphipathic character of the TT-CTL chimeric construct favors its interaction with the cell membrane of antigen presenting cells, therefore, facilitating its cytosolic delivery for class I presentation. These findings highlight the importance of antigen structure for the in vivo induction of CTL responses and may have implications for the design of synthetic peptide vaccines.

Amino Acid Sequence↗
PubMed1996

High thermal stability and cold-denaturation of an artificial polypeptide.

An amphipathic polypeptide, Pn, with a tandemly repeated LKELPEKL sequence including a proline every eight residues, as well as a series of shorter peptides having the same sequence, P2, P3, P4, P5 and P6, were synthesized. Their conformation in aqueous solution was mainly studied by CD. At low temperature, these peptides and polypeptides are completely unordered and undergo a reversible transition leading to a partly alpha-helical structure upon heating. Such behavior has been demonstrated for a few proteins by other authors and has been called cold-denaturation. The transition temperature of the polypeptide is close to 20 degrees C. The conformational change does not depend on concentration, indicating a monomolecular process. The high-temperature structure seems to be compact as for globular proteins. A model of folded structure is proposed from experimental data and from molecular modelling studies.

Cold Temperature↗
PubMed1996

[Deep morphea-type lesions, first manifestations of lymphocytic lymphoma].

INTRODUCTION: The association between scleroderma and lymphoma is uncommon and can sometimes query an fortuitous association. More particular are observations where chronological and histological features show an evident link between a tumorous process and sclerosis. OBSERVATION: This case concerns a man 69 years old who was treated for one year for partial subcutaneous sclerosis present on his legs, thighs, fore-arms, and on the upper part of the trunk. No signs were present of visceral involvement evoking a systemic scleroderma and histology showed an intrication of a deep sclerosis, fasciitis and a tumoral lymphoma process. Diagnosis of lymphocytic lymphoma was confirmed. Initiating a chemotherapy (CHOP) allowed for a reduction of the sclerosis which didn't respond to the only corticotherapy. DISCUSSION: This observation can be linked to the association of fasciitis and lymphoma identified by Naschitz et al, but is different by: 1) the clinical aspect which correspond more to deep morphea lesions; 2) the histological link between sclerosis and lymphoma. This last point suggest that it is the tumoral population which have induced the sclerosis process linked to the secretion of pro-inflammatory factors. In adverse cases with longer delay between lymphoma and scleroderma this association may be fortuitous.

Aged↗
PubMed1995

Purification of synthetic peptide libraries by affinity chromatography using the avidin-biotin system.

The specific interaction between biotin and avidin was exploited in the affinity purification of solid-phase synthesized peptide libraries. During peptide library synthesis, by means of the single-resin method in which coupling on variable positions is carried out using an equimolar mixture of amino acids, biotin was used to cap the unreacted amino groups remaining after coupling of the equimolar amino acid mixture. The following synthesis and deprotection procedures were performed as usual in tert,-butyloxycarbonyl chemistry. The purification of the peptide mixture containing N-biotinylated sequences was performed by affinity chromatography on an avidin-agarose column. The unwanted terminated sequences were retained in the avidin column while the purified peptide mixture was eluted as indicated by reverse-phase HPLC and MS analysis monitoring. The avidin column was regenerated and the biotinylated sequences were released under reversible denaturing conditions. The usefulness of biotinylation for peptide library purification is demonstrated here for the first time for a peptide mixture containing by-products that cannot be separated from the mixture by classical HPLC purification. This purification technique could be applied to all syntheses, presenting difficult reacting steps.

Amino Acid Sequence↗
PubMed1994

Influence of the conformation of a macromolecule on the generation of T-cell proliferative response. A study with model polypeptides.

To study the influence of the conformation of polypeptidic macromolecules on the generation of T-cell epitopes, sequential polypeptides with an octamer repeat unit were designed and synthesized. They adopt mainly unordered and alpha-helical conformations. Among these polypeptides, those containing proline are fully or partly unordered, and are more effective at inducing T-cell proliferation than a proline-free very stable alpha-helical polypeptide. This extremely stable alpha-helical conformation, probably stabilized by aggregation, would enhance its stability against proteolytic processing.

Amino Acid Sequence↗
PubMed1990

[Anatomy today].

Explore the source record for details and available documents.

Aging↗
PubMed1989

Neutralization of cholera toxin by rat IgA secretory antibodies induced by a free synthetic peptide.

Secretory immunoglobulin A (sIgA) is the major immunoglobulin in the bile of several species. They contribute to local immune defences of the gut. The protection against cholera toxin (CT) is due to the presence of specific sIgA in the bile and in the gut. We have already reported that oral administration of the peptide corresponding to the sequence 50-75 of cholera toxin B subunit elicits serum antibodies neutralizing CT activity, and that IgA and local protection are observed in the intestine of P50-75 orally immunized mice. In this study, we demonstrate the potential of this synthetic peptide as immunogen without carrier or adjuvant, not only in a strain known to be sensitive to CT, but also in an outbred one. Furthermore, this peptide stimulates the mucosal immunity, since we show that P50-75 induced-sIgA purified from rats bile and serum, are capable of neutralizing CT activity in the in vivo intestinal ligated loop test.

Animals↗
PubMed1989

Oral immunization with a free peptide from cholera toxin: local protection and IgA production.

It is frequently of great benefit for good protection against pathogens to elicit a local immunization. For example the importance of antibacterial as well as antitoxin local secretory IgA, for protection against cholera, has been underlined in several studies. We have already reported that oral administration of the peptide corresponding to the 50-75 sequence of cholera toxin (CT) B subunit elicits serum antibodies neutralizing CT activity. In this study we demonstrate that IgA with specificity to CT are present in intestinal secretions of mice immunized orally with the P50-75 or P30-50 peptides of CT B subunit. In addition local protection is observed in the intestine of P50-75 orally immunized mice. These results point out the potential of synthetic peptides as immunogens at the mucosal level.

Administration, Oral↗