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)

Protein Rou is a human IgA2 myeloma protein that carries the isoallotype marker n A2m(2). Partial amino acid sequence of its H chain (alpha) shows that the hinge region and the CH2 domain are homologous to alpha 2-chain and the CH1 and the CH3 domains homologous to alpha 1. Moreover, the CH1 domain contains the H-L disulfide bond identical to alpha 1. It is concluded that Rou H chain is a hybrid molecule caused by a recombination between alpha 1 and alpha 2 genes. The recombination event occurred between alpha 1-exon 1 and alpha 2-exon hinge and corresponds to position 222-223 of the alpha-chain.
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PMID:Protein Rou. A human IgA hybrid. 312 51

In the present study we have investigated whether bovine erythrocytes (Eb) specifically sensitized with human polyclonal IgA1 (Eb-IgA1) are able to bind to resident adherent rat peritoneal cells (PM phi). Rat PM phi formed rosettes with Eb-IgA1 at room temperature and at 37 degrees. The formation of these rosettes could be blocked completely by excess human serum IgA or myeloma IgA1. In contrast, human IgG or rat IgG did not inhibit the formation of rosettes, whereas human polymeric myeloma IgA2 only partially inhibited rosette formation. Complete inhibition of rosette formation was also induced by rat monomeric and polymeric myeloma IgA, suggesting species interchangeability. Furthermore, rosette formation could be completely blocked in the presence of excess asialofetuin or D-galactose, while excess ovalbumin or D-mannose had no effect. These results suggest that the oligosaccharides in the hinge region of human IgA1 are involved in the binding of Eb-IgA1 to rat PM phi.
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PMID:Binding of human IgA1 to rat peritoneal macrophages. 339 40

Immunoglobulin A1 (IgA1) proteases may be important virulence factors of certain bacteria involved in the pathogenesis of meningitis, gonorrhea, destructive periodontal diseases, and some other infections affecting mucosal membranes. This study evaluated the antigen-binding activity of free Fab alpha fragments released from human myeloma IgA1 by IgA1 protease from Haemophilus influenzae. Six myeloma proteins with antibody activity against streptolysin O, alpha-staphylolysin, or streptococcal hyaluronidase were used. Complete cleavage of the IgA1 myeloma proteins in the hinge region of the heavy chain did not affect their antigen-binding capacity. The titers of neutralizing activity associated with free Fab alpha fragments were not significantly different from those of the intact IgA1 proteins. The retained antigen-binding capacity of cleaved IgA1 is an important factor in the understanding of how IgA1 proteases may interfere with the immune protection of mucosal membranes.
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PMID:Retained antigen-binding activity of Fab alpha fragments of human monoclonal immunoglobulin A1 (IgA1) cleaved by IgA1 protease. 351 53

Fc receptors (FcR) on U937, HL-60, ML-1, and K562 cells were characterized by using competitive binding assays and EA rosette inhibition studies. Like human monocytes, U937, HL-60, and ML-1 cells bound monomeric human IgG Fc with high affinity and mildly reduced and alkylated human IgG and Fc with a somewhat diminished affinity. In contrast, K562 cells had a much lower affinity for monomeric human IgG or Fc. Concentrations of these proteins as high as 10(-5) M were needed to completely block EA rosette formation. There was no binding of reduced and alkylated IgG and Fc. We assessed the influence of various segments of IgG on FcR interactions by using human pFc', rabbit Facb, mouse IgG2b-IgG2a hybrid Ig, and also studied the effect of reduction of the interchain disulfide bonds. The FcR on all four cell types bound rabbit IgG but not rabbit Facb or human pFc', suggesting that rabbit C gamma 3 domains are required for FcR interaction and that isolated human C gamma 3 domains do not have a human FcR binding site. Murine IgG2a, but not IgG2b, was cytophilic for U937, HL-60, and ML-1 cells. Binding studies with the use of several mouse myeloma variant Ig molecules having hybrid gamma 2b-gamma 2a heavy chains showed that variants with a complete gamma 2a Fc region bound to these FcR-like IgG2a, whereas those having gamma 2a sequences only in the C gamma 3 region and in a short adjacent segment of the C gamma 2 region behaved like IgG2b and did not bind. These results suggested that additional murine gamma 2a sequences are required for FcR binding. Interestingly, the Fc fragments from murine proteins with a complete gamma 2a Fc region bound only to a limited extent. These fragments are shorter than the human IgG1 Fc fragments, and they lack that segment of the hinge region that includes the interchain disulfide bonds. Cleavage of the interchain disulfide bonds of murine Ig having a complete gamma 2a Fc region diminished binding to a similar extent as that observed with human IgG. Together, these findings provide additional insight into the roles of the hinge, C gamma 2, and C gamma 3 regions of human, rabbit, and mouse IgG in their interaction with the FcR of human tumor cells.
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PMID:Structural requirements of immunoglobulin G for binding to the Fc gamma receptors of the human tumor cell lines U937, HL-60, ML-1, and K562. 386 May 63

The structure of six human myeloma proteins: IgG1(Bal), IgG2(Klu), IgG3(Bak), IgG3(Het), IgG4(Kov) and IgG4(Pol), was studied in solution using small-angle X-ray scattering and hydrodynamic methods. For IgG1(Bal) and IgG3(Het) the experimental data, including radius of gyration (Rg degree), radii of gyration of the cross-section (Rq1, Rq2), intrinsic viscosity [eta], sedimentation coefficient (S degree 20,w) and molecular mass, were interpreted in terms of structural models based on the Fab and Fc conformations, observed in crystal, by varying the relative positions of the Fab and Fc parts, i.e. their relative angles and distances. The values Rg degree = (6.00 +/- 0.05) nm, S degree 20,w = (6.81 +/- 0.10) S and [eta] = 0.0062 +/- 0.0005 cm3/mg obtained for IgG1(Bal) are compatible with a planar model in which the angle between the Fab arms is about 120 degrees. For IgG3(Het) the following data were obtained: Rg degree = (4.90 +/- 0.05) nm, S degree 20,w = (6.32 +/- 0.01) S and [eta] = (0.0065 +/- 0.0005) cm3/mg. The apparent contradiction between the higher molecular mass and lower Rg degree and S degree 20,w values for IgG3(Het) in comparison to IgG1(Bal) can be resolved by proposing a 'non-planar' (tetrahedral) molecular shape, in which the long hinge peptide is in a folded conformation and the two Fab and Fc parts are in a closely packed arrangement. In this model the angle between the two Fab arms is about 90 degrees, in the average position. The X-ray scattering and hydrodynamic behaviour of the IgG2 and IgG4 types of antibodies appeared to be similar to IgG1(Bal). The parameters of the two IgG3 proteins are similar while they are different to the others.
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PMID:Conformation of human IgG subclasses in solution. Small-angle X-ray scattering and hydrodynamic studies. 397 74

IgA protease, a proteolytic enzyme found in human saliva and colonic fluid, hydrolyzes human serum IgA immunoglobulins to yield Fab(alpha) and Fc(alpha) fragments. The enzyme is produced by organisms in the normal human microflora and can be purified from culture filtrates of the common human oral organism Streptococcus sanguis (American Type Culture Collection no. 10556). IgA protease is inactive against all other protein substrates examined including the other classes of human immunoglobulins. The role of this enzyme in affecting the function of the secretory IgA immune system is unknown. To further characterize and explain this unusual substrate specificity, the susceptibility of 31 human IgA myeloma proteins of both subclasses was investigated. 16 IgA1 and 15 IgA2 myeloma paraproteins were treated with enzyme and the extent of proteolysis was determined by cellulose actate electrophoresis, immunoelectrophoresis, polyacrylamide gel electrophoresis, and column chromatography. All IgA1 proteins were enzymatically cleaved to Fab(alpha) and Fc(alpha) fragments, but all IgA2 proteins were resistant, yielding no fragments after prolonged enzymatic treatment. N-terminal amino acid sequence analysis of the purified Fc(alpha) fragment of a single IgA1 paraprotein was as follows: Thr-Pro-Ser-Pro-?-Thr-Pro-Pro-Thr-Pro-Ser-Pro-Ser. Comparison of this sequence to that reported for the IgA1 heavy chain shows that the enzyme-susceptible peptide bond is a Pro-Thr in the IgA1 hinge region. The most likely explanation of the resistance of the IgA2 subclass to IgA protease is a deletion in the heavy chain which commences with the critical threonine of the susceptible Pro-Thr bond.
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PMID:Differential susceptibility of human IgA immunoglobulins to streptococcal IgA protease. 443 34

The aminoacid sequence of the "hinge" region of two human IgA(1) myeloma proteins was found to be identical. A 30-residue fragment contains 3 cysteines, 12 prolines, and carbohydrate, and the sequence of a small segment of the hinge region is repeated at least twice. Since a deletion of 12-13 residues was found in the same region of an IgA(2) myeloma protein, it is possible that IgA(1) molecules are the result of the insertion of a partially duplicated gene segment in the immunoglobulin genes.
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PMID:Partial duplication in the "hinge" region of IgA 1 myeloma proteins. 450 29

Two monoclonal IgG3 (kappa) antibodies against murine Thy-1.2 antigen produced by murine 1B5 and 1aG4/C5 hybridomas were partially characterized. The 1aG4/C5 antibody has slightly higher affinity for the Thy-1.2 antigen in binding tests and more efficiently kills the Thy-1.2+ thymocytes in cytotoxicity assays as compared to the 1B5 antibody. The latter, in addition, reacts significantly with the Thy-1.1 antigen (the allelic form of Thy-1 antigen expressed on the cells of the donor of the immune cells. Both monoclonal antibodies exhibit some characteristic properties of IgG3 of myeloma origin, e.g. a tendency to aggregation, high pI and interaction with protein A. Our monoclonal antibodies are sensitive to pepsin digestion, resistant to trypsin, their disulphide bonds are rapidly cleaved by sulphitolysis and reduction by dithiothreitol. They possess characteristic acidic peptides bearing the disulphide bonds between the heavy chains. These antibodies, however, differ to some extent from each other in some properties (precipitation with staphylococcal protein A, solubility, pI, electrophoretic behaviour of the light chains). They possess different heavy chain peptides bearing the interchain disulphide bonds and thus they probably differ in the hinge region. This structural difference may be associated with different sensitivity of these two antibodies to sulphitolysis and proteolysis.
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PMID:Monoclonal IgG3 (kappa) antibodies against murine Thy-1.2 antigen produced by murine hybridomas. Differences in the specificity of the antigen binding site and in the structure of the hinge region. 618 35

The conformation of the hinge region of the human IgG1 immunoglobulin has been investigated by making use of His-224 in the hinge region as a built-in proton nuclear magnetic resonance (NMR) probe. Human myeloma IgG1 (kappa) proteins Ogo and Yot and human polyclonal IgG were used along with their Fab and F(ab')2 fragments for the assignment of the His-224 signals. The titration behavior of His-224 of the intact IgG and the fragments was compared. It was shown that the titration curves for the intact IgG and the F(ab')2 fragments are identical and quite similar to those for the histidine residue in small peptides. By contrast, the Fab fragments give titration curves which are quite different from those for the intact IgG and the F(ab')2 fragments. Conclusions derived may be summarized as follows: (1) in the intact IgG1, the hinge peptide is fully exposed to the solvent and exhibits internal motion which is much more rapid than the Fab segmental motion with respect to Fc: (2) at the loss of the Fc portion of the IgG, the conformation of the hinge peptide in the F(ab')2 fragments remains unchanged; (3) the heavy--heavy interchain interactions involving the two disulfide bridges do not play the primary role in determining the conformation of the hinge region in the intact IgG as well as in the F(ab')2 fragments; (4) the existence of a small stretch of peptide fragment Thr-225--Leu-234 is essential in maintaining the conformation of the hinge region of the intact IgG and the F(ab')2 fragments; (5) in the Fab fragments, as a result of cleavage of a major portion of the hinge peptide, the C-terminal part of the heavy chain including His-224 is partially folded back toward the globular portion of the polypeptide chains; and (6) the hinge peptide in the Fab fragments still retains a degree of flexibility which is similar to that in the intact IgG and the F(ab')2 fragments.
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PMID:Proton nuclear magnetic resonance studies of human immunoglobulins: conformation of the hinge region of the IgG1 immunoglobulin. 625 77

The expressed immunoglobulin heavy chain genes of five gamma 2b-gamma 2a hybrid chain-producing variants of the mouse myeloma MPC-11 (gamma 2b, kappa) have been characterized by genomic Southern blot analysis. Results show that a hybrid gamma 2b-gamma 2a gene was formed in each variant by recombination between the expressed gamma 2b gene of MPC-11 and a gamma 2a gene. The recombination sites are within regions of marked homology between gamma 2b and gamma 2a genes: at least three and probably four variants show gamma 2b-gamma 2a recombination within the heavy chain constant region 2 (CH2) domain, while the fifth has its recombination site between the penultimate nucleotide of CH1 and the eighth nucleotide of the hinge. An unexpected finding is that the hybrid heavy chain-producing variants fall into two subgroups based on their use of different gamma 2a gene forms in hybrid gene formation. This result leads to the speculation that either a tandem gamma 2a gene duplication was present in MPC-11 prior to variant generation or mitotic recombination between chromosomes occurred in the generation of one variant subgroup. The similarity of hybrid gene formation in MPC-11 variants to that apparently responsible for concerted evolution within multigene families and hybrid protein expression in various individuals is noted, and the possible relationship between hybrid gene formation and the heavy chain class switch is discussed.
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PMID:Hybrid gamma 2b-gamma 2a genes expressed in myeloma variants: evidence for homologous recombination. 631 38


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