Search PubMed⌕ Search

Biomedical subjects

A Saul

Publications and source records attributed to A Saul.

174 records · Page 10Linked to original sources
PubMedDate not supplied

The molecular specificity of linear B-epitopes in the E7 open reading frame protein of human papillomavirus 16 defined by monoclonal antibodies.

Human papillomavirus (HPV) 16 is highly associated with premalignant and malignant anogenital epithelial lesions. The transforming function resides within the viral E7 open reading frame protein. We have defined three immunodominant linear B-epitopes in the E7 protein. In the present study, we determine the contribution of individual amino acid residues to antibody binding of these three epitopes using replacement set analysis. In this approach, each epitope residue is substituted in turn by each of the other 19 genetically encoded amino acids to produce analogues which are tested for specific monoclonal antibody binding. We demonstrate the specificity of the monoclonal antibodies for epitopes of HPV 16 E7 in binding studies using synthetic epitope analogues of other HPV genotypes. Comparison between HPV 16 and other HPV genotypes suggests that variability in amino acid composition at the E7 epitopic sites does not appear to be host-antibody driven.

Amino Acid Sequence↗
PubMedDate not supplied

High titer response against a malarial antigen depends on the flanking sequence of the immunizing peptide conjugate.

The immunogenicity of peptides conjugates containing the epitope STNS, recognized by inhibitory monoclonal antibodies directed against the Plasmodium falciparum merozoite surface antigen MSA2, was investigated. The sequence of the flanking regions was critical in determining the response against the central epitope. In the best immunogen tested, this flanking sequence was not related to the sequence of the surface antigen itself but nevertheless gave rise to a strong anti-MSA2 protein response as judged by Western blotting and immunofluorescence. This finding illustrates the importance of defining such flanking sequences in optimizing peptide based vaccines.

Animals↗
PubMedDate not supplied

[Are there subpolar tuberculoid cases?].

The idea of the existence of subpolar tuberculoid cases is supported on the spectral conception of Ridley and Jopling who included the subpolar lepromatous patients between LL and BL cases. According with Languillon, we have studied 40 tuberculoid cases to find out clinical, bacteriological, immunological and histopathological parameters of subpolar T cases. The subpolar T cases do exist, they are unstable cases which can slide through the immunological spectrum towards the L pole. These cases are characterized by numerous, symmetrical, dysesthetic tuberculoid lesions with an important neural involvement. Bacilli can be found in a small number in the smears of nasal mucosae in some cases. Mitsuda reaction is always positive and histopathologically the granulomas, lymphocytes and epithelioid cells are in less number without the epidermotropism which is very often seen in polar T cases.

Adolescent↗
PubMedDate not supplied

Peptides for inducing cross-reactive anti-malarial antibodies.

Immunological cross-reactions between malarial proteins are frequently observed. This paper describes an approach to generate such antibody responses that target many parasite proteins using a limited number of peptides as immunogens. Peptides used contained a known epitope, NKND, that is common to many malarial proteins or combinations of tri-peptides which are commonly present in parasite proteins. One of the two NKND-containing peptides elicited antibodies reacting to six parasite proteins and fusion proteins containing NKND. The antibody specificity was directed to NKND. Two of the four combination peptides were recognized by hyperimmune human sera and mouse immune serum in vitro, and one elicited antibodies recognizing parasites on immunofluorescence assay.

Amino Acid Sequence↗
PubMedDate not supplied

The influence of water-miscible alcohols on the conformation of antibodies directed against a defined epitope.

Antiserum was raised against peptide P513 (CSQRSTNSAST) conjugated to diphtheria toxoid. P513 is a sequence derived from the Plasmodium falciparum merozoite surface antigen (MSA-2) containing the STNS epitope recognized by antibodies that inhibit parasite growth. Although antibodies directed against other STNS-containing peptides can bind to the native MSA-2 antigen, polyclonal anti-P513 serum failed to react in immunofluorescence assays with parasites or with MSA-2 by Western blotting. However, addition of methanol, ethanol or 1-propanol modified the specificity of the anti-P513 interaction, resulting in recognition of MSA-2. The effect was concentration dependent: at high alcohol concentrations, the specificity was further modified, and a previously undescribed rhoptry antigen was recognized. These results indicate that addition of alcohols to immunoassays may provide a way of modifying the specificity of antibodies in general, and the reactivity of anti-peptide serum with the parent protein in particular.

1-Propanol↗
PubMedDate not supplied

Antimycobacterial antibodies in diffuse lepromatous leprosy detected by counterimmunoelectrophoresis.

By using the counterimmunoelectrophoresis (CIE) technic it was possible to demonstrate the presence of antimycobacterial antibodies in the sera of patients suffering from lepromatous leprosy. The antigen was prepared from isolated Mycobacterium lepraemurium. The technic was more reliable and quicker than Ouchterlony's classical double diffusion in gel. Clinical application of the method is therefore recommended.

Antibodies, Bacterial↗
PubMedDate not supplied

Two immunogenic peptide conjugates derived from P. falciparum MSA2 give rise to antibodies that crossreact with a nonhomologous 195-kDa malarial protein.

Merzoite Surface Antigen 2 (MSA2) is a 51-kDa antigen from P. falciparum that has marked sequence variation between malarial strains but contains highly conserved N- and C-terminal sequences. Previously described peptide sequences from these conserved domains are capable, when coupled to the carrier protein diphtheria toxoid (DT), of raising antibodies that recognize MSA2 in a number of malarial isolates. In this study we report the existence of two peptide conjugates from the conserved C-terminus of MSA2 which, when used as immunogens, produce antibodies that react with a 195-kDa protein and give a merzoite surface pattern on immunofluorescence assay (IFA). The antisera against these peptide conjugates do not recognize MSA2; however, the 195-kDa protein, and identical surface pattern on IFA, is recognized by a monoclonal antibody (mAB) against Merzoite Surface Antigen 1 (MSA1). These two peptides, when unconjugated to DT, are nonimmunogenic, and DT alone is not capable of inducing antibodies that react with malarial proteins. The combination of the carrier and either peptide is capable, however, of raising antibodies against MSA1, despite sharing no sequence homology with this antigen. This data thus highlights the importance of protein conformation when generating antibody against carrier-peptide conjugates.

Amino Acid Sequence↗
PubMedDate not supplied

Mapping a conserved conformational epitope from the M protein of group A streptococci.

The carboxyl terminus of the M protein of group A streptococci (GAS) is highly conserved and contains epitopes that have been shown to induce opsonic antibodies and protection against GAS infection. This region of the protein can also stimulate T cells, which can react in vitro with heart antigens. Since different segments of the carboxyl terminus may be involved in immunity to GAS and in the pathogenesis of autoimmune disease (rheumatic heart disease), it is important to precisely define critical epitopes. However, the M protein is known to be a coiled coil, and a critical immunodominant antibody-binding epitope within this region (peptide 145, a 20-mer with the sequence LRRDLDASREAKK-QVEKALE) is shown here to be conformational. Thus, small synthetic overlapping peptides of 8-12 amino acids in length that span peptide 145 (p145) were unable to capture antibodies present in p145-immune mouse sera or in endemic human sera, even though antibodies raised to these small peptides coupled to diphtheria toxoid could bind the smaller peptides and, in some cases, p145. A series of mutated peptides in which every residue of p145 was sequentially altered also failed to identify critical residues for antibody binding. We thus devised a strategy to produce chimeric peptides in which small peptides copying the M protein sequence were displayed within a larger 28-mer peptide derived from the sequence of the GCN4 leucine zipper DNA binding protein of yeast. A 12-amino-acid window of the p145 sequence was inserted into the GCN4 peptide in such a way as to preserve any potential helical structure. The window was moved along one residue at a time to give a series of peptides representing p145. Circular dichroism demonstrated that these larger chimeric peptides and p145, but not a shorter 12-mer peptide, displayed alpha-helical potential in 50% trifluoroethanol. Certain chimeric peptides efficiently captured antibodies specific for p145 and thus enabled us to map the minimal antibody-binding sequence. RRDLDASREAKK, referred to as J(1)2. The chimeric peptide containing this sequence, referred to as J2, was able to inhibit opsonization of GAS by human antisera containing anti-peptide 145 antibodies. The T-cell response from p145-immunized responder B10.BR mice to J2 and J(I)2 was much lower than the response to p145 and mapped to a different peptide.

Animals↗