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 amino acid sequences of most of the CH1, CH2 and CH3 domains of IgG Zie, a myeloma protein belonging to the IgG2 subclass, are presented. These data make possible a comparison of the sequences of residues 253-446 of all four subclasses of immunoglobulins: these residues make up almost the entire Fc regions. A comparison can also be made of the CH1 domain of IgG1 Eu and the CH1 domain of IgG2 Zie. Earlier sequence analyses of the Fc regions of subclass 1 and 3 proteins, and parts of the Fc regions of subclass 2 and 4 proteins showed that about 95% of these sequences were identical. The extended comparisons made possible by the data presented here show that this very high degree of identity is maintained throughout the four subclasses. Similarly, the CH1 domains of gamma 1 and gamma 2 chains were found to have about 93% sequence identity. It is unlikely that the few single amino acid changes within the constant region domains can account for the marked differences between subclasses observed in the region domains can account for the marked differences between subclasses observed in the biological effector functions of immunoglobulin Fc regions, especially since most of the changes are highly conservative. Rather, it seems probable that these functional differences are caused by conformational differences between the subgroups, which result from sequence differences in the hinge regions.
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PMID:The amino acid sequences of the three heavy chain constant region domains of a human IgG2 myeloma protein. 11 60

DNA from newborn mice was digested with restriction endonuclease EcoRI, and a 6.6-kilobase fragment encoding immunoglobulin gamma 2b chain mRNA derived from MPC 11 myeloma was enriched about 100-fold by RPC-5 column chromatography and agarose gell electrophoresis. The 6.6-kilobase fragment was cloned with lambda gt WES.lambda B as EK2 vector. The cloned phage (lambda WES.IgH22) contained the constant region gene of the gamma 2b chain but not the variable region gene of MPC 11 mRNA. The constant region genes of the other gamma chains (i.e., gamma 1, gamma 2a, and gamma 3) were not present in lambda gt WES.IgH22 DNA. R-loop mapping indicates that the gamma 2b chain structural gene is divided into two parts (330 +/- 60 SD base pairs and 930 +/- 110 SD base pairs) by an intervening sequence (360 +/- 100 SD base pairs). The nucleotide sequence around the junction of the hinge region and CH2 domain was determined and shown to match the amino acid sequence of the initial part of the CH2 domain of the gamma 2b chain. The base sequence upstream from the junction, however, is unrelated to the amino acid sequence of the CH1 domain and the hinge region of all the gamma chains whose sequences have been determined. These results indicate that the gamma 2b chain gene is interrupted at the junction of the hinge region and CH2 domain by an intervening sequence. The existence of two more intervening sequences, one between the CH1 domain and the hinge region and the other between the CH2 and CH3 domains, is discussed.
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PMID:Cloning immunoglobulin gamma 2b chain gene of mouse: characterization and partial sequence determination. 11 31

Recent studies of the micron- and kappa-chains of the first patient (GLI) with micronHCD indicated that the observed defect was the result of the failure of assembly of the intact kappa-chain to the micron-chain, which lacked the VH domain but had the CH1 Cys normally linked to the light chain. To explore the possibility that the VH region is necessary for the formation of the HL disulfide bond, in vitro studies were performed with GLI micron- and kappa-chains and with the CH1 domain and kappa-chain derived from an IgG3 myeloma protein, KUP, which yields separate VH, CH1, and kappa-chains after papain digestion and reduction. The proteins were reduced and allowed to reoxidize, and the combination products were assessed by gel chromatography under dissociating conditions by SDS-PAGE and by immunoprecipitation techniques. The results suggest that, although in vitro covalent and noncovalent combinations are possible between intact light chains and their autologous heavy chains even in the absence of the VH domain, the efficiency is less than that when the intact Fd region is used. Hence, it seems likely that lack of VH alone is not sufficient to explain the failure of assembly observed in muHCD.
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PMID:The interaction of immunoglobulin heavy and light chains in the absence of the VH domain. 40 2

A unique case of gamma3 heavy chain disease with two related serum proteins is reported. One molecule appears to be an IgG3lambda myeloma protein. The second molecule is a dimer of a shortened gamma3 heavy chain that has an unblocked amino terminus and lacks the VH and CH1 domains. Its probable origin as a synthetic product is discussed. The clinical and pathologic features of this patient resemble those of other patients with gamma heavy chain disease more than those of patients with multiple myeloma. It seems likely that the heavy chain disease protein is the result of a mutational event in the malignant clone originally producing the myeloma protein.
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PMID:An unusual case of a plasma cell neoplasm with an IgG3lambda myeloma and a gamma3 heavy chain disease protein. 41 32

The digestion of a human IgG1 K myeloma protein with pepsin in the presence of 8M-urea was observed to produce a fragment, designated Fb'2, which differed from the products of aqueous peptic digestion and from other characteristic immunoglobulin digestion products. 2. Fragment Fb's was also found when two other IgG1/K proteins were treated similarly. 3. Sedimentation-equilibrium studies showed the mol.wt. of fragment Fb'2 to be 56800. 4. On reduction, two equivalents of each of three peptides were released from fragment Fb's; these were characterized by N- and C-terminal determinations and by amino acid sequencing. 5. Fragment Fb'2 was shown to consist of the constant regions of both light chains, from residue Ile-117 to the C-terminus, and the CH1 domains and hinge region of the heavy chains, from residue Val-113 to residue Met-252, with a gap of five residues within the intrachain disulphide loop, between residues Leu-174 and Tyr-180.
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PMID:Fb'2, a new peptic fragment of human immunoglobulin G. 77 69

The digestion of human IgG1/K myeloma proteins with pepsin in the presence of 8 M-urea produces fragments that differ from those produced by aqueous peptic digestion, and from other characteristic immunoglobulin fragments. Fb'2, the larger urea/pepsin fragment, was previously shown to consist of the constant regions of the light chains, and the CH1 domains and hinge regions of the heavy chains. The smaller fragment, upFc, has now been characterized. After reduction, three peptides were released from fragment upFc. Amino acid sequencing, N- and C-terminal determinations and amino acid compositions have enabled these peptides to be identified as residues Ile-253 to Leu-306, residues Thr-307 to Asp-376 and residues Thr-411 to Gly-446 of the heavy chain. Fragment upFc therefore contains the entire Fc region, beginning at residue Ile-253, except for a 34-residue section from within the CH3-domain disulphide loop. Peptic digestion of IgG1/K proteins in 8M-urea therefore provides a method for isolating from gamma1 heavy chains five homogeneous peptides in good yield, which account for almost the entire constant region. Characterization of fragments Fb'2 and upFc has shown that the action of pepsin in urea is entirely different from that of aqueous pepsin. Two gamma1 heavy chains have been shown to differ in sequence at three positions from the sequence reported for protein Eu.
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PMID:Characterization of upFc, a fragment of human immunoglobulin G1 produced by pepsin in urea. 79 Dec 67

Earlier studies on antisera against Fab of pooled human IgG and IgA myeloma proteins disclosed the presence of class-specific Fd antibodies, the demonstration of which required interaction of heavy and light chains. To extend our knowledge about the antigenic structure of the Fd fragment of human immunoglobulins, antisera were prepared in rabbits against gamma chains of pooled IgG and of four IgG1 myeloma proteins, and Fd gamma fragment and a cyanogen bromide-produced CH1 preparation of an IgG1 myeloma protein, and an Fd' alpha fragment of an IgA1 myeloma protein. No antigenic determinants exclusively confined to the CH1 region of intact human IgG could be demonstrated with these antisera. The antigenic structure of CH1 intact immunoglobulins may thus only be defined by light-chain-dependent determinants.
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PMID:Studies on fd fragments of human immunoglobulins. III. Immunogenic properties of gamma chains, myeloma fd gamma, and myeloma fd1 alpha. 80 61

A mutant cell line (IF2) derived from the mouse myeloma MOPC 21 has been used for the isolation and sequence analysis of H-chain mRNA. The IF2 cells synthesise an H-chain of reduced size in which the CH1 homology region is missing. Sizing of the IF2 H-chain mRNA and wild-type H-chain mRNA revealed that the deletion is expressed at the mRNA level. The mutant H-chain mRNA sedimented at 16-S, enabling effective resolution from 18-S ribosomal RNA. In experiments using IF2 cells labelled with [32P]phosphate, the 16-S mRNA was purified by oligo(T)-cellulose chromatography. Polyacrylamide gel analysis of the poly(A)-containing fraction showed the presence of a single radioactive band. Comparison of the mobility of this band relative to markers of known molecular weight revealed that the molecule contained about 1600 nucleotides. Digestion of the 32-P-labelled mRNA with T1 ribonuclease and two-dimensional fractionation of the resulting oligonucleotides yielded a 'finger-print' suitable for a preliminary sequence analysis. By using the established amino acid sequence of the IF2 H-chain and a knowledge of the genetic code, 14 oligonucleotides were assigned within the constant region and four within the variable region of the IF2 H-chain. This sequence data accounts for 19.5% of the coding region. Several other oligonucleotides, which could not be assigned within the coding region but which occurred in approximately molar yield, have also been partially characterised. These oligonucleotides are presumably derived from the untranslated regions of mRNA.
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PMID:Purification and sequence analysis of the mRNA coding for an immunoglobulin heavy chain. 81 96

We have developed an efficient system for obtaining myeloma mutants defective in trans-acting factors required for immunoglobulin (Ig) gene expression. The system consists of a myeloma cell line designed for this purpose and an efficient method for selecting mutants from it. The cell line is X63.653 transfected with the mu gene, whose tailpiece sequence was replaced with the transmembrane sequence of human EGF receptor to hold mu on the cell surface and whose CH1 sequence was removed to prevent mu from being retained in the endoplasmic reticulum. It efficiently and stably expressed mu chains of IgM on the cell surface (mu m+) without light chains. To obtain mutants lacking mu m (mu m-) from the mu m+ cell line by selectively killing mu m+ cells, a method with ricin A-conjugated anti-mu antibody was more reliable than complement lysis mediated by anti-mu antibody. Applying the system, we obtained a variety of mu m- mutants.
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PMID:Efficient selection of mu m-mutants from mu m-expressing myeloma cells by treatment with ricin A-conjugated anti-mu antibody. 128 53

A genetic construct was created incorporating gene fragments encoding the H chain V region of the human carcinoma specific antibody L6, the CH1 domain of human IgG1, a linker region, and human IL-2. This construct was cotransfected with a chimeric L6 L chain construct into the murine myeloma cell line Ag8.653 for expression. First round clones produced the fusion protein at an estimated 5 to 10 micrograms/ml based on idiotypic reactivity. Dual binding activity was demonstrated through specific interaction with the L6 Ag on human tumor cells and the IL-2R on activated human T cells. The IL-2 portion of the molecule was shown to support the growth of the IL-2-dependent T cell line CTLL2, and the qualitative nature of the IL-2 signal was found to be the same as rIL-2 with respect to induction of tyrosine-phosphorylation of intracellular protein substrates. Tumor cells coated with the fusion protein were shown to cause T cell proliferation and the presence of the fusion protein was found to enhance cell-mediated destruction of human tumor cells.
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PMID:Genetic construction and characterization of a fusion protein consisting of a chimeric F(ab') with specificity for carcinomas and human IL-2. 170 2


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