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)

The specificities of the combining sites of 19 mouse monoclonal antibodies to dextran B1355S have been characterized immunochemically by quantitative precipitin and precipitin inhibition assays; association constants for B1355S were determined by affinity gel electrophoresis. Cross-reactive and individual idiotypes related to the BALB/c B1355S-binding myeloma proteins MOPC104E [IdI(MOPC104E)] and J558 [IdI(J558)], determined by a radioimmunoassay, and heavy-chain variable-region sequences, are presented. Antibodies to B1355S are "alpha (1----3) alpha (1----6)-specific" as determined by precipitin and precipitin inhibition assays with dextrans and oligosaccharides, respectively, containing alternating alpha (1----3) alpha (1----6) linkages compared with oligosaccharides composed solely of alpha (1----3) or alpha (1----6) linkages; all antibodies have low association constants (less than or equal to 10(5) ml/g). However, there is also considerable diversity among the proteins as seen in the five groups of different patterns of reactivity with numerous dextrans having different structures, and the variability in affinity even among antibodies showing the same fine specificity by precipitin assay. There is little observable correlation of heavy-chain variable-region amino-acid sequence with specificity or affinity; however, all proteins having D-region amino acids Tyr,Asp at positions 96,97 express the MOPC104E individual idiotype and belong to precipitin specificity group 5, the group most cross-reactive with numerous dextrans, whereas those proteins having the J558 individual idiotype, Arg,Tyr or Asn,Tyr at 96,97 are found in all five precipitin groups.
Mol Immunol 1986 Apr
PMID:Immunochemical studies of mouse monoclonal antibodies to dextran B1355S--II. Combining site specificity, sequence, idiotype and affinity. 242 50

The amino acid sequences of the constant regions of rabbit kappa light chains (C kappa) are remarkably divergent. The K1 allotypes differ at 47 of 106 positions; the K1 and K2 isotypes differ at three additional positions. Variability and structural dissimilarity plots reveal that most of these differences occur in clusters. Major hydrophilic areas are also found near some of these clusters. The structures of rabbit C kappa are modeled using the known alpha-carbon backbone structure of the Fab fragment of mouse myeloma protein McPC603. The effect of sequence variations upon the hypothetical three-dimensional structures was assessed and immunogenic determinants predicted and located. It was found that predicted determinants were external and located in or near loops. Two clusters of potentially interacting regions were predicted. Within each there could be several "topographical" and overlapping sets of epitopes that are recognized by different antibody-combining sites. One of the predicted immunogenic sites clearly interacts with the CH1 domain of the heavy chain. A heavy-chain dependent serological determinant has been correlated with amino acid differences in this region (kappa chain positions 121 and 124).
Mol Immunol 1986 May
PMID:Localization of rabbit kappa light chain allotypic determinants. 242 35

Total cellular Poly A+ RNA from TEPC15 myeloma and murine lymphoid tissues was analyzed by denaturing agarose gel electrophoresis and Northern blot hybridization to specific heavy chain constant region cDNAs; mu, gamma 2b and alpha RNA species were identified in each of the tissues and in the IgA producing TEPC15 myeloma. In total Poly A+ RNA from TEPC15 myeloma, alpha-cDNA hybridized predominantly to a 2.3 kb RNA species; 11.5 and 4.1 kb RNA species were evident as well. Successive hybridization of the same RNA to mu- and gamma 2b-specific cDNAs demonstrated the presence of both mu and gamma 2b specific RNA species with electrophoretic mobilities apparently identical to the 11.5 and 2.3 kb RNA species identified by alpha-specific hybridization. These data establish the presence of Poly A+ RNA species containing alpha, mu, and gamma 2b sequences in TEPC15 cells and suggest the transcription of RNA from both CH-containing chromosomes in TEPC15 myeloma (one chromosome in the TEPC15 cell line contains all the CH genes while the other chromosome has deleted all CH genes except alpha). In total Poly A+ RNA from normal mouse tissues (Peyer's patch and spleen) all three cDNA probes hybridized predominantly to an 11.5 kb RNA species. Primer extension experiments demonstrated that alpha cDNA could prime for the synthesis by reverse transcriptase of gamma 2b DNA when Peyer's patch Poly A+ RNA was used as the template. This suggests the existence of a single transcript containing alpha and gamma 2b sequences. Murine lymphoid tissues contained putative mRNAs for mu, gamma 2b and alpha heavy chain proteins, whereas TEPC15 myeloma polysomal Poly A+ RNA contained only alpha mRNA.
Mol Immunol 1986 Jun
PMID:Identification of the major immunoglobulin heavy chain poly A+ RNA in murine lymphoid tissue. 242 42

Structurally diverse dextrans from Leuconostoc mesenteroides and related bacteria have been used extensively in fundamental immunochemical studies such as induction and characterization of anti-dextran antibodies, as well as in studies of their interaction with pneumococcal antisera, normal bovine serum, concanavalin A, dextran-binding myeloma immunoglobulins and hybridoma antibodies. The inherent lack of specificity of structural data obtained by POSA and general lack of insight into other limitations of these analyses has often led to inaccurate and superficial interpretations. Proper interpretation of past and future studies necessitates pointing out previous inadequacies of dextran structural data and detailing more recently acquired structural information on the dextrans. Unambiguous terminology has been achieved by a new system of linkage symbols that includes the designation of structural positions, such as (1----3; l)- and (1----3; b) as linear-chain and branch-point positions, respectively. Results of immunological studies are reviewed. Improved interpretations and correlations are made on the basis of structural data from MSA and several other techniques which have become available on the dextrans.
Mol Immunol 1986 Sep
PMID:Immunochemical and related interactions with dextrans reviewed in terms of improved structural information. 243

The specificity of 14 monoclonal antibodies has been determined by immunoblotting (IB) and haemagglutination-inhibition (HAI) analysis using IgA1 and IgA2 myeloma proteins and eight different IgA1 fragments. Two antibodies probably recognized epitopes on the CH1 domain of IgA. They reacted with all Fab-containing fragments irrespective of whether these originated from the same or different IgA proteins. Seven antibodies were directed against epitopes on the CH2 domain. These antibodies were reactive with F(abc)2 fragments. They failed to react with Fab, Fab' and F(ab')2 fragments. Two out of these seven antibodies did not react with two-chain IgA half-molecules and Fabc fragments containing a single heavy and a single light chain. This suggests that these two antibodies recognized an epitope whose structure is dependent on disulfide linked heavy chains. Five other antibodies showed specificity for the CH3 domain. They were reactive with all CH3-containing molecules, irrespective of whether they comprised one or two alpha chains. Our study demonstrates that IB is an appropriate technique to determine domain specificity of monoclonal anti-immunoglobulin reagents. Although the IB tests were performed on denatured proteins the results agreed surprisingly well with those of the HAI analyses. Moreover, the IB technique could be used on fragments which could not be purified well enough for HAI analyses.
Mol Immunol 1986 Jul
PMID:Monoclonal antibodies against different domains of human IgA: specificities determined by immunoblotting and haemagglutination-inhibition. 243 12

Thirteen monoclonal antibodies (MAbs) were produced against Lol p I (Rye I), the major Lolium perenne (rye grass) pollen allergen. Spleen cells from A/J and SJL mice immunized with highly purified Lol p I (Lol I) were allowed to fuse with cells from the non-secreting Sp2/0-Ag14 myeloma cell line. Each MAb was analyzed for antigenic specificity by radioimmunoassay (RIA) using 125I-Lol I. The epitope specificities of seven of the MAbs were examined by competitive binding against a labelled standard MAb for the Lol I antigen (Ag). The dissociation constant, Kd, of one MAb (No. 3.2) that was studied most extensively was determined by double Ab RIA to be 3.5 X 10(-6) L/M. This MAb recognized the related 27,000-30,000 Group I glycoproteins found in the pollens of nine other species of grass pollens tested, including weak binding to Bermuda grass Group I (Cyn d I), which by conventional analysis using polyclonal anti-Lol I serum shows no detectable binding. Monoclonal antibody No. 3.2 was coupled covalently to Sepharose 4B and used to prepare highly purified Lol I from a partially purified rye pollen extract. Finally, an RIA was developed which permitted the analysis of the Group I components in rye grass and nine other grass pollen species. The latter assay is likely to prove useful in the standardization of grass pollen extracts according to their Group I contents.
Mol Immunol 1986 Dec
PMID:Monoclonal antibodies to the major Lolium perenne (rye grass) pollen allergen Lol p I (Rye I). 243 41

Two anti-TNP antibodies exhibiting unusual features are described. They were obtained in two independent fusions. Spleen cells from CB20 mice sensitized with TNP-Ficoll and challenged with TNP-LPS were fused with SP2/0 myeloma cells. One of these hybridomas, CBT3, secretes antibodies which react with both monospecific anti-gamma 2b and anti-gamma 3 anti-isotypic sera; the second hybridoma, CBT4, secretes antibodies reacting with monospecific anti-mu and anti-gamma 2b sera. Only one type of immunoglobulin is secreted by each hybridoma, ruling out the hypothesis of hybrid molecules formed by distinct heavy chains. These results imply that the two heavy chains are made up from elements encoded by gamma 3 and gamma 2b genes in CBT3 and by gamma 2b and mu genes in CBT4. The molecular mechanisms underlying the production of these singular heavy chains are discussed.
Mol Immunol 1987 Jan
PMID:Hybrid polypeptide heavy chains produced by two hybridoma lines. 244 Dec 46

We examined the expression of T15 idiotopes (Id) on phosphorylcholine (PC)-binding monoclonal immunoglobulins and defined the structural correlates of these Id. The seven monoclonal anti-Id antibodies used as probes recognize distinct determinants that range from the antigen binding site to the CH1 domain on TEPC15. Competition between a series of PC-specific immunoglobulins and radiolabelled TEPC15 for binding to anti-Id in solid phase revealed a broad spectrum of idiotopic crossreactivity. A strong crossreactivity with TEPC15 was observed only in proteins possessing the VK22 light chain. Each of the seven discrete, overlapping T15 Id may be expressed independently of each other on PC-binding immunoglobulins, indicating a significant idiotopic heterogeneity among T15 B-cell clones. No correlation was found between the public (shared) expression of an Id and its position relative to the antigen-binding site. Variations in the primary sequences of PC-binding immunoglobulins were correlated with their effect on individual Id expression. Regions influencing the expression of three Id were localized on a computer display of the three-dimensional structure of the closely related PC-binding myeloma protein McPC603. These data show that some, but not all individual Id determinants may be influenced by amino acid substitutions in the first and third hypervariable loops.
Mol Immunol 1987 Jun
PMID:Serologic and molecular characterization of the T15 idiotype--II. Structural basis of independent idiotope expression on phosphorylcholine-specific monoclonal antibodies. 244 40

Nerve growth factor (NGF) was isolated from the venom of Vipera lebetina and was purified to homogeneity as judged by SDS gel electrophoresis. The biologically active NGF was used to immunize BALB/c mouse, and the spleen cells from immunized mouse were fused with mouse PAI myeloma cells. Forty-seven hybrid cell lines, secreting monoclonal antibodies to V. lebetina NGF, were isolated and nine of them purified from ascitic fluids. The isolated antibodies define two partially overlapping epitopes of the V. lebetina NGF which are not involved in the biological activity of the molecule. Both epitopes are also present on the beta-NGF from the mouse salivary gland and on the NGFs from the following snake venoms: V. lebetina, V, ursini, V, berus berus, Echis carinatus, Bungarus caeruleus, Agkistrodon halys, Naja naja oxiana, Naja naja atra and Naja naja, but not on the bovine seminal plasma NGF. The mol. wts of the NGFs in these snake venoms were determined by Western immunoblot with monoclonal antibodies. The mol. wts of the NGFs from V. ursini (37,000), E. carinatus (36,000, 44,000) and A. halys (29,000) were determined for the first time.
Mol Immunol 1987 Dec
PMID:Monoclonal antibodies against Vipera lebetina venom nerve growth factor cross-react with other snake venom nerve growth factors. 244 8

In the present investigation, we have utilized the somatic cell hybridization technique to generate an experimental model for studying the differential expression of membrane (mIg) and secreted (sIg) forms of immunoglobulin that characterize different stages of B cell development. We describe here that fusion of the dextran-binding myeloma, MOPC 104E (mu, lambda 1) and the phthalate-binding B cell hybridoma, 2C3E1 (gamma 1, kappa) results in the formation of antigen-specific, double hybrids (tribrids) that coexpress both parental secreted forms of Ig but express only one of the two possible membrane forms of immunoglobulin (Ig). This segregated expression of membrane Ig is a new and unexpected finding that has been substantiated here by both immunological and biochemical methods. Analysis by SDS-containing polyacrylamide gels (SDS-PAGE) reveals distinct and characteristic migration patterns for each of the four Ig heavy chains in the tribrids (mu membrane, mu secreted, gamma 1 membrane and gamma 1 secreted). Immunochemical analysis of the immunoglobulin from the tribrids confirms the coexpression of both secreted forms of immunoglobulin in most of the tribrid lines tested and indicates that about 30% of the tribrids express only phthalate-specific gamma 1 membrane Ig, while 38% express only dextran-binding mu membrane Ig. About 30% of the tribrids secrete both antibodies but express no membrane form and less than 1% are non-secretors. Approximately 2% initially express both membrane forms of Ig, as determined by immunocytoadherence assay using appropriate target cells but subsequently express only one membrane form during propagation in vitro. SDS-PAGE analysis of surface labeled tribrids confirms that in tribrids expressing membrane Ig, only a single mIg is synthesized. These results suggest that the expression of the secreted and membrane forms of immunoglobulin are separately regulated and the tribrids represent a model with which to study the mechanisms involved in the regulation of each structurally distinct immunoglobulin form.
Mol Immunol 1987 Dec
PMID:Expression of mu and gamma 1 membrane forms of immunoglobulin segregate in somatic cell hybrids. 244 9


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