Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monoclonal antibodies against the Shigella flexneri lipopolysaccharide (LPS) were generated in two fusions by using the myeloma cell line Sp2/0 as a fusion partner with spleen cells from BALB/c mice immunized with S. flexneri serotypes 1b and 3a bacteria. The antibodies were characterized by immunoblotting, enzyme-linked immunosorbent assay (ELISA), hemagglutination, and coagglutination. Four different types of monoclonal antibodies were isolated: antibodies specific for the core antigen of the LPS, antibodies specific for the type I O antigen, antibodies specific for the group 6 O antigen, and antibodies specific for the type III:6,7,8 O antigen. The core-specific antibodies were shown to be specific for the Escherichia coli R3 core, which all S. flexneri LPSs tested, except for S. flexneri serotype 6 LPS, have. The type I O antigen-specific antibodies were shown to bind exclusively to S. flexneri serotypes 1a and 1b in ELISA. The type III:6,7,8 O-antigen-specific antibodies were specific for S. flexneri serotype 3a in ELISA and hemagglutination. Two different group 6 O-antigen-specific antibodies were bound. One was bound in both ELISA and hemagglutination to LPSs of S. flexneri serotypes 1b, 3a, 3b, and 4b, whereas the second was bound only to LPSs of serotypes 3a, 3b, and 4b in ELISA but to LPSs of all four serotypes in hemagglutination. The specificity of the isolated I, III:6,7,8, and group 6 monoclonal antibodies was verified by coagglutination of 363 S. flexneri clinical isolates.
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PMID:Monoclonal antibodies specific for Shigella flexneri lipopolysaccharides: clones binding to type I and type III:6,7,8 antigens, group 6 antigen, and a core epitope. 242 39

Hybrid cells producing monoclonal antibodies against the O-antigens of Shigella flexneri were obtained by polyethylene glycol-mediated fusion of myeloma cells and lymphocytes from BALB/c mice immunized with whole heat-killed S. flexneri bacteria of serotypes 2a and 2b. Clones were selected for their binding specificity to structurally defined S. flexneri lipopolysaccharides (LPS). The following three groups were identified as recognizing three different epitopes: monoclonal antibodies binding to (i) S. flexneri LPS with the II:3,4 antigens, (ii) S. flexneri LPS with the II:3,4 antigens and the II:7,8 antigens, and (iii) S. flexneri LPS with the 7,8 group antigen only. Of cloned and characterized antibodies, more than 90% had either the mu or gamma 3 heavy chain and 98% had the kappa light chain. The exquisite specificity of each monoclonal antibody preparation was in complete contrast to the polyclonal specificities seen in sera from immunized rabbits. Even absorbed rabbit S. flexneri typing sera contained antibodies reacting with several different LPS, i.e., they were not type antigen specific. Ascites from immunoglobulin G monoclonal antibody preparations representing the three different specificities were used for sensitizing Staphylococcus aureus Cowan 1 bacteria and were used in coagglutination. In testing 211 clinical isolates of all different serotypes of S. flexneri, the reagents were shown to be sensitive and specific in correctly identifying all S. flexneri II and 7,8 antigen-containing strains with no false positives. Two isolated immunoglobulin M antibody clones specific for the II:3,4 and 7,8 antigens were used as successfully for identification by direct slide agglutination. These results suggest that the monoclonal reagents are superior to conventional typing antisera.
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PMID:Monoclonal antibodies specific for O-antigenic polysaccharides of Shigella flexneri: clones binding to II, II:3,4, and 7,8 epitopes. 619 76

To determine the role of humoral mucosal immune response in protection against shigellosis, we have obtained a monoclonal dimeric immunoglobulin A (IgA) antibody specific for Shigella flexneri serotype 5a lipopolysaccharide (mIgA) and used a murine pulmonary infection model that mimics the lesions occurring in natural intestinal infection. Adult BALB/c mice challenged with 10(7) S. flexneri organisms developed a rapid inflammatory response characterized by polymorphonuclear cell infiltration around and within the bronchi and strong systemic interleukin 6 response. Implantation of hybridoma cells in the back of mice, resulting in the development of a myeloma tumor producing mIgA in the serum and subsequently secretory mIgA in local secretions, or direct intranasal administration of these antibodies, protected the animals against subsequent intranasal challenge with S. flexneri serotype 5a. Absence of histopathological lesion and significant decrease in bacterial load of the lungs and of systemic interleukin 6 response were the three major criteria of protection. This protection was shown to be serotype-specific and dependent on local concentration of mIgA. These data demonstrate that mucosal antibodies directed against a single polysaccharidic surface epitope of Shigella can protect against the disease.
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PMID:Monoclonal immunoglobulin A antibody directed against serotype-specific epitope of Shigella flexneri lipopolysaccharide protects against murine experimental shigellosis. 754 97

Oral administration of rabbit secretory IgA (sIgA) to adult BALB/c mice induced IgA+, IgM+, and IgG+ lymphoblasts in the Peyer's patches, whose fusion with myeloma cells resulted in hybridomas producing IgA, IgM, and IgG1 antibodies to the secretory component (SC). This suggests that SC could serve as a vector to target protective epitopes into mucosal lymphoid tissue and elicit an immune response. We tested this concept by inserting a Shigella flexneri invasin B epitope into SC, which, following reassociation with IgA, was delivered orally to mice. To identify potential insertion sites at the surface of SC, we constructed a molecular model of the first and second Ig-like domains of rabbit SC. A surface epitope recognized by an SC-specific antibody was mapped to the loop connecting the E and F beta strands of domain I. This 8-amino acid sequence was replaced by a 9-amino acid linear epitope from S. flexneri invasin B. We found that cellular trafficking of recombinant SC produced in mammalian CV-1 cells was drastically altered and resulted in a 50-fold lower rate of secretion. However, purification of chimeric SC could be achieved by Ni2+-chelate affinity chromatoraphy. Both wild-type and chimeric SC bound to dimeric IgA, but not to monomeric IgA. Reconstituted sIgA carrying the invasin B epitope within the SC moiety triggers the appearance of seric and salivary invasin B-specific antibodies. Thus, neo-antigenized sIgA can serve as a mucosal vaccine delivery system inducing systemic and mucosal immune responses.
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PMID:A pathogen-specific epitope inserted into recombinant secretory immunoglobulin A is immunogenic by the oral route. 896 37