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

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

We have cloned a rearranged immunoglobulin heavy chain variable (VH) region gene (NL-1-H-5) from the cells of a mouse hybridoma, NL-1, which produce a monoclonal antibody against the common acute lymphocytic leukemia (cALL) antigen. The DNA base sequence of NL-1-H-5 clone revealed that the VH region gene of NL-1 cells used the identical or closely related leader (L) and VH gene to those of the myeloma cell line MOPC-21. There were seven base differences, and six of them were found in the second complementary-determining hypervariable region (CDR-2). The five nucleotide differences in CDR-2 resulted in the variation of amino acid residues of positions 54, 56, 58, and 59. In particular, nucleotide changes at position 56 and 59 yielded tyrosine residues which might be involved in a part of the antibody-combining site structure for cALL antigen.
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PMID:The antibody molecule to common acute lymphocytic leukemia (cALL) antigen used the identical or closely related VH gene segment as that of MOPC-21 immunoglobulin heavy chain. 315 8

In order to prepare an antibody directed at the common amino acid sequence of mammalian, avian, and fish luteinizing hormone-releasing hormones (LHRHs), C-terminal free LHRH was conjugated with bovine thyroglobulin, and was used as the antigen. A monoclonal antibody (LRH13) was obtained as an ascitic fluid by fusing the spleen cells of a BALB/c donor mouse immunized with the antigen to X63.Ag8.653 mouse myeloma cells followed by limiting dilution cloning and transplanting a positive clone to BALB/c mice. This monoclonal antibody seems to belong to IgG2b as it was eluted from protein A-Sepharose CL-4B with citrate buffer pH 3.5. competitive binding experiment using fragment peptides of LHRH indicated the binding site of LRH13 was a region around serine and tyrosine, and modification of mammalian LHRH by radioiodination caused a marked decrease in the binding activity. LRH13 has an affinity constant of 0.134 X 10(9) M-1 to native mammalian LHRH, and binds C-terminal free LHRH with a similar affinity (1.6X), however, it binds with higher affinities to N- and C-terminal free LHRH (12.9X), N-terminal free LHRH (10.4X), salmon LHRH (8.3X) and chicken LHRH-I (6.0X). Chicken LHRH-II, where tyrosine is replaced for histidine, has a lower affinity (0.3X) than that of mammalian LHRH. From its high affinity to N-, C-terminal free LHRH, LRH13 is also expected to bind possible precursor peptides of LHRH. Immunohistochemical staining of the brain sections obtained from rats, mice, chickens, Japanese quail, and rainbow trout successfully visualized cell bodies and fibers distributed from the olfactory bulb to the median eminence, indicating high LHRH specificity and wide crossreactivity in animal classes of this monoclonal antibody. With this antibody, LHRH-like immunoreactive substance in the pineal gland was also stained with fixation at neutral pH.
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PMID:Preparation of a monoclonal antibody to common amino acid sequence of LHRH and its application. 353 Jul 29

Previous work has shown that IgG rheumatoid factors (RF) bind to the C gamma 2-C gamma 3 interface region of human IgG in the same area that binds staphylococcal protein A (SPA). Group A, C, and G strains of Streptococci possess Fc receptors that bind to IgG but not to fragments containing only the C gamma 2 or C gamma 3 domains. This work describes the binding site location on human IgG for the binding of the isolated Fc receptor from the T15 strain of a Group A streptococcus and its relationship to the site that binds SPA and the IgG RF. The isolated T15 Fc receptor (T15) with a molecular mass of 29.5 kD inhibited the binding of IgG RF to IgG. The binding of T15 itself to IgG was strongly inhibited by SPA (42.0 kD) and its monovalent fragment D (7 kD). Human IgG fragments consisting of the C gamma 3 domains did not inhibit the binding of T15 to IgG, whereas those with both domains were effective inhibitors. T15 did not bind to rabbit IgG fragments consisting of either the C gamma 2 or C gamma 3 domains, but did bind to those with both domains. An IgG3 myeloma protein was a poor inhibitor and has been shown to bind poorly to the IgG RF. Most IgG3 myeloma proteins did not bind to SPA. The substitution of Arg and Phe for His 435 and Tyr 436 is responsible for the poor binding of IgG3 to SPA and to the IgG RF. Chemical modification of His or Tyr on IgG reduced its ability to inhibit the binding of T15 to IgG. Reversal of the chemical modifications with hydroxylamine resulted in near complete restoration of inhibitory capacity. This information, collectively, coupled with the known positions in space of the His and Tyr residues in the C gamma 2-C gamma 3 interface region, verified that both His 435 and Tyr 436, and possibly His 310 and 433, are involved. These residues are also involved in binding SPA and the IgG RF. These data therefore indicate that the T15 Group A Streptococcal Fc receptor binds to the same location on the Fc of IgG as SPA and the IgG RF. The biologic relevance of these similarities between bacterial cell wall Fc receptors and IgG RF are not yet apparent, but suggest that RF could bear the internal image of these bacterial structures.
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PMID:T15 group A streptococcal Fc receptor binds to the same location on IgG as staphylococcal protein A and IgG rheumatoid factors. 354 19

Two peptides, P123 and P124, representing amino acid sequences His 542-Lys 557 and Tyr 459-Arg 472, respectively, of the CH4 domain of rat IgE and predicted to be located on accessible regions of the protein were synthesized by a solid-phase procedure. Rabbits were immunized with the peptides conjugated to KLH and their antisera were tested for reactivity with free peptide and rat IgE by inhibition-ELISA. Each animal produced antibodies which reacted specifically with its immunizing peptide (titre greater than 1/62,500), but not with other synthetic peptides of similar chain-length and composition. Antisera directed against peptides P123 and P124 specifically bound purified rat IgE (IR 162) and IgE in whole myeloma serum (greater than 1/6400), but showed no reaction with normal rat serum proteins and only very low binding to purified human IgE. In addition the binding of anti-peptide sera to rat IgE could be completely inhibited with either homologous peptide or purified rat IgE, but not by other peptides or purified human IgE. Heating rat IgE for 1 hr at 56 degrees C enhanced its binding to anti-peptide antibodies by between 4- and 60-fold, but markedly reduced its reactivity with a rabbit anti-rat IgE (Fc) serum. These results suggest that antibodies directed against the synthetic peptides employed recognize and specifically bind to sites within the CH4 domain of rat IgE represented by their respective immunizing peptides. Furthermore, these antibodies are capable of detecting subtle alterations in structural conformation resulting from heating at 56 degrees C. Epitopes represented by peptides P123 and P124 may contribute to the heat-sensitive cytophilic region of rat IgE.
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PMID:Use of synthetic peptides in the production and characterization of antibodies directed against predetermined specificities in rat immunoglobulin E. 370 75

The amino-acid sequence Phe-Tyr-Met-Glu is unique to phosphorylcholine (PC)-binding antibodies. It occurs in the first complementarity-determining region (CDR1) of the immunoglobulin heavy chains in 89% of all the anti-PC myeloma and hybridoma proteins but is not present in 490 other immunoglobulin heavy chains, 854 light chains or in 2,260 other unrelated proteins. This unique tetrapeptide therefore seems to be involved in PC binding. Here we compare the effectiveness of Phe-Tyr-Met-Glu and other structurally related peptides in inhibiting the binding of PC to PC-binding proteins McPC603 and HOPC8. We also test a surface-simulation peptide that was constructed to mimic the combining site of McPC603. Our data suggest that all these peptides inhibit the binding of PC to PC-binding proteins non-specifically and we show by computer modelling that the surface-simulation peptide does not duplicate the combining site of McPC603.
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PMID:Inhibition of phosphorylcholine binding to antibodies using synthetic peptides. 380 74

In order to obtain detailed information about the relationship between structure and function in antibody molecules, a method called affinity labeling has been devised to attach chemical labels specifically to amino acid residues in the active sites of antibody molecules. With antibodies to three different haptens, highly specific labeling of the active sites has been achieved. Tyrosine residues on both heavy and light polypeptide chains have been labeled in a molar ratio close to 2:1, and labels on the two chains are equally specific to the active sites. Peptide fragmentation studies of the labeled chains of one antibody system have shown that: (i) within 25 amino acid residues of the labeled tyrosine on either chain, substantial chemical heterogeneity exists among different antibody molecules of the same specificity; and (ii) the labeled peptide fragments from both chains are very similar in physicochemical characteristics, including average size, heterogeneity, and unusual hydrophobicity. These experimental results have led us to the view that a particular region of the heavy chain and a particular region of the light chain are utilized to construct the active sites of the three different antibodies, differences in specificity arising from chemical perturbations in these two regions. Correlated structural studies of affinity-labeled antibodies and of the homogeneous light chains (Bence Jones proteins) and heavy chains produced in multiple myeloma may permit the identification of these special active-site regions. The view that active sites of different specificity are chemical perturbations of a particular region of the antibody molecule has a possible close analogue in enzyme systems, particularly among the esterases. The marked chemical similarities we have observed between the active site regions of heavy and light chains indicate to us that chemical homologies, but not identities, exist between the chains. This is reinforced by recently obtained amino acid sequence data which reveal homologies between the two chains near their carboxyl-terminals. These results indicate that the structural genes which code for the synthesis of heavy and light chains are related, presumably having arisen from some common ancestral gene during evolution. This conclusion strongly suggests that both heavy and light chains determine antibody specificity, and has important implications for the still-unknow mechanisms of antibody biosynthesis.
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PMID:Antibody active sites and immunoglobulin molecules. 416 Sep 42

The gammaA myeloma protein 315 from the mouse was affinity-labeled with m-nitrobenzene diazonium fluoroborate which, as shown previously, leads to selective modification of the tyrosine at position 34 in the light chains of this protein. The azotyrosine bond was reduced with dithionite to form 3-aminotyrosine. The aryl amino group of the aminotyrosine was selectively reacted with the bifunctional reagent 1,5-difluoro-2,4-dinitrobenzene. Cross-links were formed between the aminotyrosine and at least two residues-one on the same light chain and one in the Fd region of the heavy chain. Since affinity labeling of various antibodies with diazonium reagents has frequently led to azotyrosine formation, the approach described in this paper should have general applicability.
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PMID:Site-directed cross-linking: a new approach to mapping antibody combining sites. 528 29

A mouse myeloma protein of the immunoglobulin A class, which specifically binds dinitrophenyl ligands, has been successfully affinity labeled (site-directed labeling) with several diazonium reagents, leading to inactivation of the combining sites. The labeling reagents reacted only with tyrosine residues of light chain origin. The 7S subunit of the myeloma protein appears to contain only one reactive site.
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PMID:Affinity site labeling of a mouse myeloma protein which binds dinitrophenyl ligands. 569 57


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