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 presence of aberrant lambda 1 light (L) chain fragment (lambda 1 F) on the secreted myeloma protein of MOPC-315 has been demonstrated by serological and immunochemical methods. We developed a highly sensitive radioimmunoassay that utilizes exquisitely specific xenogeneic anti-lambda 1 antibodies to detect the minute amounts of lambda 1 F on lambda 2-bearing MOPC-315 myeloma proteins. In addition, structural evidence that lambda 1 F is present on MOPC-315 myeloma protein was demonstrated by subjecting 125I-labeled MOPC-315 myeloma protein to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions followed by autoradiography. The relative amounts of lambda 1 F and lambda 2-chain on MOPC-315 myeloma were measured by two independent methods. The molar ratio of lambda 1 F to lambda 2 was calculated to be 1:68 by radioimmunoassay and 1:80 by analytical SDS-PAGE. This represents the first demonstration that an aberrant L-chain fragment combines with a heavy chain and is secreted in association with antigen-binding myeloma proteins. The implications of these results on L-chain isotype exclusion are discussed.
Mol Immunol 1986 Jan
PMID:Lack of isotype exclusion and expression of aberrant lambda light chain on secreted MOPC-315 myeloma proteins. 308 41

An IgGl(lambda) Mot myeloma protein showed a unique susceptibility toward papain digestion. The Fab fragment of Mot was more digestible with papain than the Fc fragment. This phenomenon was found to occur by unusual cleavage of the Fd fragment with papain. Determination of the complete primary structure of the V region of the H chain of Mot identified two papain cleavage sites in the second complementarity-determining region (CDR). Amino acid sequence of the cleavage sites was Ser(55)-Asp-Asp-Argdecrease-Thr-Thr-Tyr-Gly-Pro-Argdecrease- Ser-Gln- (decrease = cleavage site). In the vicinity of these cleavage sites, many hydrophilic and polar residues are present and the predicted secondary structure near these cleavage sites suggested that this region was exposed on the surface of the molecule, and that the unusual papain cleavage of the IgG Mot might be caused by a unique conformation of the molecule, making it highly susceptible to enzyme digestion.
Mol Immunol 1986 Feb
PMID:Amino acid sequence of the variable region of heavy chain in immunoglobulin (Mot) having unusual papain cleavage sites. 308 50

The crystal structure of the Fab of McPC603, a phosphocholine-binding mouse myeloma protein, has been refined at 2.7 A resolution by a combination of restrained least-squares refinement and molecular modeling. The overall structure remains as previously reported, with an elbow bend angle between the variable and constant modules of 133 degrees. Some adjustments have been made in the structure of the loops as a result of the refinement. The hypervariable loops are all visible in the electron density map with the exception of three residues in the first hypervariable loop of the light chain. A sulfate ion occupies the site of binding of the phosphate moiety of phosphocholine.
J Mol Biol 1986 Aug 20
PMID:Phosphocholine binding immunoglobulin Fab McPC603. An X-ray diffraction study at 2.7 A. 309 27

The mouse immunoglobulin heavy-chain mu constant region gene was cloned into the early region 1B of an adenovirus type 5 vector to allow reproducible kinetics of expression of the mu gene in the presence of continuous host protein synthesis after infection by the recombinant. The immunoglobulin-adenovirus recombinant is helper independent in infecting human fibroblastic and B- and T-cell lines and expresses mu in a cell-type-specific manner. By Northern blot analysis, correctly polyadenylated and spliced E1B-mu S and E1B-mu m mRNAs are found to be equally abundant at steady state in fibroblasts. In contrast, and appropriately, only E1B-mu S mRNAs accumulate in a lambda light-chain-secreting myeloma cell line. Analysis of nascent transcripts pulse labeled in isolated nuclei demonstrates equimolar polymerase loading throughout the mu region in all cell types infected by mu-Ad. Thus, correct polyadenylation and splicing of E1B-mu S and E1B-mu m in fibroblasts does not require transcription termination in the region separating the mu S and mu m polyadenylation sites. Furthermore, differential expression of mu transcripts in the background of myeloma cells is regulated at the level of RNA processing and does not require the presence of the immunoglobulin heavy-chain enhancer or promoter element.
Mol Cell Biol 1986 Jan
PMID:Cell-type-specific synthesis of murine immunoglobulin mu RNA from an adenovirus vector. 309 1

The VL amino acid sequence of an anti-lysozyme hybridoma protein, HyHEL-5, was determined. HyHEL-5 expresses a V region of the VK4 family and JK1. The VK4 family also includes light chains from galactan binding antibodies, although sequence comparisons suggest that a different member of this family is used to encode HyHEL-5. The HyHEL-5 light chain has a deletion of residue 96, such that L3 is one residue shorter than the majority of murine L3. Chain recombination experiments, employing H and L chains from different anti-galactan and anti-lysozyme binding antibodies, were performed to examine the contribution of the H and L chain in dictating specificity for either galactan or the lysozyme epitope recognized by HyHEL-5. The results indicate that, although the ability to bind galactan vs lysozyme is absolutely heavy-chain dependent, having the appropriate heavy chain is not sufficient for specific high affinity binding. Both the L chains from HyHEL-5 and J539 (a galactan-binding myeloma protein) were capable of supporting binding to galactan in combination with the J539 H chain, but affinity for galactan is less with the HyHEL-5 L chain. Only VK4 L chains supported binding of the HyHEL-5 heavy chain to the HyHEL-5 epitope, although binding with the J539 L chain was low affinity and relatively nonspecific.
Mol Immunol 1986 Sep
PMID:Contribution of the VK4 light chain to antibody specificity for lysozyme and beta (1,6)D-galactan. 309 19

The investigation of 750 B-lymphocyte hybridoma clones obtained by fusion of mouse myeloma and newborn heterozygous Igk-la/Igk-1b rat splenocytes has revealed that 9,8% of Ig kappa-chain genes are rearranged productively. Seventeen hybridomas secrete kappa-chains of both allelic variants. The analysis of IgM molecules of nine such clones demonstrated that in six cases only one L-chain allotype is present in IgM. Thus for the first time the high frequency of selective association of H and L chains was shown. Evidently this selectively may function as one of the allelic exclusion mechanisms at the Ig assembly stage.
Mol Biol (Mosk)
PMID:[Analysis of the frequency of allelic exclusion of immunoglobulin light chain genes and molecular characteristics of immunoglobulins secreted by hybridomas with expression of both allelic genes]. 310 Sep 44

Adherent hybrids between immunoglobulin-producing mouse myeloma cells and fibroblasts do not produce immunoglobulin polypeptide chains. These hybrids retained the actively rearranged immunoglobulin genes of the myeloma parental cells but lacked immunoglobulin heavy- and light-chain RNA transcripts. We conclude that the shutoff of immunoglobulin production in these hybrids occurs at the transcription or early processing level.
Mol Cell Biol 1987 Feb
PMID:Extinction of expression of immunoglobulin genes in myeloma X fibroblast somatic cell hybrids. 310 48

Amino terminal amino acid sequences were obtained for both the heavy (H) and light (L) chains of seven BALB/c anti-arsonate (Ar) monoclonal antibodies representing the 5AF6 and 3C6 idiotype (id) families described in this strain. 5AF6 family H chains showed strong homology to the germ-line gene sequence for the A strain 36-60 family. However, four to five identical H chain sequence differences for two of these antibodies (5AF6 and 95B5), as well as two previously reported related sequences (92D5, 94B10), suggested they were encoded by a different Vh. The 36-60 family Vh genes have been shown to be identical to the Vh gene of the anti-DNP binding myeloma M460 [Dzierzak et al., J. Immun. 136, 1864-1870 (1986)]. H chains amino acid sequences derived from an id-460+ anti-DNP hybridoma and a germ-line gene differing from the 30-60-like Vh sequence [Dzierzak et al., J. Immun. 136, 1864-1870 (1986)] were found to be virtually identical to the 95B5 and 5AF6 Vh sequences. This suggests that the same two related H chains making up two subsets of the 5AF6 anti-Ar id family are also both used in two subsets of the id-460 anti-DNP response. 5AF6 family L chains were highly homologous to the other Vk2 L chains of the 36-60 family. 3C6 family H chains can be placed in the Vh l group, are unrelated to the described anti-Ar H chain families, and have been placed in a new anti-Ar Vh family, Ars-E. The 3C6 H is similar, however, to a Vh used by a BALB/c anti-GAT idiotype family of antibodies. 3C6 L chains were of the murine kappa chain group, Vk8 and most resembled an L chain from an A strain monoclonal anti-Ar having no defined idiotype.
Mol Immunol 1987 Apr
PMID:Two BALB/c anti-arsonate idiotype families: two heavy chain variable regions (Vh) shared with anti-DNP antibodies are used by one family while a Vh similar to anti-GAT antibodies is used by the other. 311 3

The genome of hybridoma PTF-02 has two genes for the kappa chains, and only one of these codes for the synthesis of the antibody light chains. The nucleotide sequences corresponding to the leader peptide and to the variable region of this gene were determined. An amino acid sequence corresponding to exons has been proposed on the basis of the nucleotide sequence. A nucleotide sequence adjacent to the gene at the 5'-end has also been determined, in particular, the precise localization of TATA- and CAT-boxes as well as those of the conservative deca (dc) and pentadeca (pd) sequences. The structure of the regulatory region in the gene is similar to that in the myeloma genomes. However, the 5'-region differs in its nucleotide composition and in the frequency of dc sequences from the DNA sequences adjacent to the 5'-end of eukaryotic genes which do not belong to the immunoglobulin family.
Mol Biol (Mosk)
PMID:[The structure of the variable gene for the kappa chains of antibodies produced by hybridoma PTF-02]. 311 99

Monoclonal antibodies to chicken riboflavin carrier protein have been produced by fusing immunized mouse spleen cells with myeloma SP2/O-Ag 14. The three different monoclonal antibodies specifically bound 125I-labelled chicken riboflavin carrier protein and were characterized with respect to their affinities to bind the antigen, subclass and isotype. These three monoclonal antibodies had similar affinities for holo-, apo- and SDS-denatured riboflavin carrier protein but were unable to recognize the reduced and carboxymethylated protein indicating that they were directed to specific conformational epitopes on the native avian protein. Succinylation of the vitamin carrier protein while still retaining flavin binding characteristics totally abolished the cross-reactivity with all the three monoclonal antibodies indicating that lysine residues were involved at the antigenic sites of the protein. This shows that the antigenic loci may be distinct from the flavin binding sites in the protein. All three antibodies were able to recognize riboflavin carrier protein present in the sera of pregnant rats, monkeys and humans indicating that the epitopes to which they are directed are conserved throughout evolution. These antibodies can therefore be effectively used for radioimmunoassays and further studies on the functional aspects of this protein in higher mammals.
Mol Immunol 1987 Sep
PMID:Immunological characterization of riboflavin carrier proteins using monoclonal antibodies. 311 15


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