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)

In the present study we have investigated the structure of the helper T cell (Th)-defined idiotope (Id) of myeloma protein 315 lambda 2 light chain (lambda 2(315] in BALB/c (H-2d) mice which carry a high-responder immune response gene for this Id. Three peptides were synthesized which spanned the third hypervariable region (HV3) of lambda 2(315): peptides 88-99, 94-108 and 91-108. Only peptide 91-108 was capable of eliciting carrier-specific Th that recognized M315 or free lambda 2(315). These Th did not recognize lambda 2(5-7) chain which differs from lambda 2(315) at 4 positions in this region; these are Tyr94, Ser95, Thr96, Tyr98 for lambda 2(5-7) and Phe94, Arg95, Asn96, Phe98 for lambda 2(315). Immunization with peptide analogues revealed that substitution of Tyr for Phe94 was compatible with Id-lambda 2(315) mimicry, but substitution of Ser for Arg95 or Thr for Asn96 destroyed the Th-recognized Id. Furthermore, Th primed with lambda 2(5-7) chain did not cross-react with lambda 2T952; these lambda 2 chains only differ from each other at positions 98 and 99 at the V lambda 2-J lambda 2 junction. The data indicate that individual amino acids of short peptide segments are critical for Th-recognized Id of the lambda 2 HV3 loop and V lambda 2-J lambda 2 junction. Furthermore, the immunogenicity of a small peptide suggests that the carrier (lambda 2)-specific Th recognize Id that have been processed by antigen-presenting cells (APC). This implies the existence of two categories of "internal images" of foreign or of self antigens: (a) serologically defined and (b) T lymphocyte defined. We propose that as a rule, Id processing by APC, including B cells, destroys the first and reveals the second category. The possible physiological function of these Id-specific T cells in network interactions with B cells is discussed.
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PMID:The T lymphocyte response to syngeneic lambda 2 light chain idiotopes. Significance of individual amino acids revealed by variant lambda 2 chains and idiotope-mimicking chemically synthesized peptides. 294 95

In an attempt to understand the relationship of amino acid sequence to the formation of primary or multiple myeloma-related amyloid (AL amyloid), we have determined the complete amino acid sequence of amyloid protein BAN. This protein belongs to the kappa I immunoglobulin light chain subgroup and has a polypeptide chain length of 126 amino acids. It encompasses the entire variable region, the joining segment and the first tryptic peptide of the constant region. This protein has two unique features. First, the molecule is glycosylated. At position 61 the usual arginine residue has been replaced by an asparagine with the generation of the signal sequence Asn-Phe-Thr, to which a glucosamine-containing carbohydrate unit is attached. Secondly, the protein is not monoclonal but consists of two chains which have the same variable region but different J-segments. Comparison of the BAN sequence with other amyloid and nonamyloid kappa I proteins reveals a systematic difference between the two groups. In the amyloid proteins, several hydrophilic framework residues have been replaced by hydrophobic residues. These substitutions may provide the nucleation sites for self-aggregation and fibril formation.
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PMID:Polymorphism in a kappa I primary (AL) amyloid protein (BAN). 308 40

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.
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PMID:Amino acid sequence of the variable region of heavy chain in immunoglobulin (Mot) having unusual papain cleavage sites. 308 50

Concanavalin A binding to glycoprotein bands on nitrocellulose blots was used to detect mannose, sorbose, N-acetylgalactosamine and/or glucose residues on 100% (31/31) of human Bence Jones protein light chains, following sodium dodecyl sulphate-polyacrylamide gel electrophoresis. All (20/20) light chains form IgG myeloma proteins and light chains from a preparation of normal polyclonal human IgG were also bound by concanavalin A. The specificity of concanavalin A for glycoproteins was demonstrated by its binding to human Fc fragments and a human monoclonal anti-Rhesus D antibody (REG-A), but not to human albumin pFc' fragments and aglycosylated REG-A derived from cells grown in the presence of the glycosylation inhibitor tunicamycin. These results suggest that all Bence Jones proteins and light chains from myeloma IgG proteins contain mono- or oligosaccharides linked O-glycosidically to serine or threonine residues.
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PMID:Immunogenicity and antigenicity of immunoglobulins: detection of human immunoglobulin light-chain carbohydrate, using concanavalin A. 311 95

1. Peptide maps of Fc fragments or heavy chains of 36 G myeloma proteins and two "heavy chain disease" proteins belonging to the four gamma-chain subgroups revealed very striking similarities between them. However differences in a few peptides were noted. This was most pronounced for the Ge(gamma(2)d) subgroup which lacked three peptides characteristic of the other three subgroups. While Fc fragments from different proteins belonging to the same subgroup appeared very similar, minor differences in addition to those based on currently recognized Gm factors were occasionally noted. 2. Fc fragments from Gm(a+) We(gamma(2)b) proteins had a peptide previously shown to be characteristic of normal Gm(a+) gammaG-globulins. Fc fragments from Gm(a-) molecules belonging to the We(gamma(2)b), Vi(gamma(2)c), or Ne(gamma(2)a) subgroups, whether Gm(b+), Gm(f+), or Gm(-), had the peptide previously identified in Gm(b+f+) normal gammaG-globulin. This "non-a" peptide was absent in peptide maps from Gm(-) molecules of the Ge(gamma(2)d) subgroup which contained instead another peptide with the same electrophoretic mobility but migrating slightly further on chromatography. 3. Both the "a" and "non-a" peptides were pentapeptides having three amino acids in common, and differing in the other two. The "a" peptide contained one residue of lysine, aspartic acid, threonine, leucine, and glutamic acid. The "non-a" peptides prepared from Gm(b+), Gm(f+), and Gm(-) proteins were identical and contained one residue of lysine, threonine, and methionine sulfone, and two residues of glutamic acid. 4. Several possible mechanisms for the origin of these differences, and their possible role in serologic specificity are discussed.
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PMID:Structural studies of human gamma-G-myeloma proteins of different antigenic subgroups and genetic specificities. 416 48

Approximately 15 per cent of the light chains from homogeneous immunoglobulins in patients with multiple myeloma contain an oligosaccharide group. Five human myeloma light chains that contained carbohydrate were studied. The sequence Asn-[unk]-Ser/Thr was at the site of carbohydrate attachment in all light chains. The carbohydrate group was attached to the asparagine residue of this triplet sequence which in all five light chains was located in the variable region. The occasional occurrence of carbohydrate in myeloma light chains is seen as the consequence of a variable region mutation creating an Asn-[unk]-Ser/Thr sequence to which carbohydrate is attached by an enzyme capable of recognizing the characteristic triplet sequence.
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PMID:Attachment of carbohydrate to the variable region of myeloma immunoglobulin light chains. 419 90

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

Glycopeptides have been isolated from tryptic digests of kappa-type light chains separated from human myeloma proteins obtained from the serum of two patients, Car and Rai. The glycopeptides are derived from the variable region of the chain in both cases, but from different sections. On the basis of homology it is deduced that glycopeptide from Car, kappaI type, is derived from position 25-31 whereas that from Rai, kappaII type, is from position 62-77, their sequences being respectively Ala-Ser-Gln-Asn-Ile-Ser and Phe-Ser-Gly-Ser-Gly-Ser-Gly(Thr,Asp)Phe-Thr-Leu-Asx-Ile-Ser-Arg. The significance of the results is discussed in connexion with the nature of the attachment site of carbohydrate to protein.
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PMID:Glycopeptides from human kappa-chains. 511 28

The hyalin material in massive cutaneous hyalinosis, a disease characterized by extensive tumorous periodic acid-Schiff-(PAS) positive extracellular cutaneous deposits, has been elucidated by biochemical and immunologic methods. Three major components were found: kappa light chains, a mannose-rich glycoprotein, and type I collagen. Trace amounts of fibrinogen, fibronectin, laminin, IgG, pregnancy-specific glycoprotein, albumin, and keratan sulfate, but not keratin, were also present. The kappa light chains were monoclonal, cryoprecipiting, and more basic than the kappa chains from two myeloma patients. The glycoprotein, which could not be identified as any known glycoprotein, had an apparent molecular weight of 90,000 D. Amino acid analysis showed that glutamic acid, aspartic acid, leucine, and threonine were abundant, whereas hydroxyproline, hydroxylysine, and sulfhydryl amino acids were absent. The carbohydrate content of the protein was approximately 20%. The major monosaccharides were mannose and N-acetylglucosamine. Galactose, N-acetylneuraminic acid and fucose also were present. The third major component of the hyalin material was identified as type I collagen. A humoral immune response to the storage material was found: the patient's serum contained IgM and IgG class antibodies against the mannosylglycoprotein (90 kD glycoprotein) and against type I collagen.
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PMID:Massive cutaneous hyalinosis. Identification of the hyalin material as monoclonal kappa light chains, adhesive 90 kD glycoprotein, and type I collagen. 620 74

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


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