Heavy Chains Of Human Immunoglobulins Research Articles

Transcriptomic response of rat hippocampus and spleen cells to single and chronic administration of the peptide selank

A new direction in designing new drugs able to effectively reduce anxiety without having side effects is the use of endogenous regulatory peptides. Research� ers of the Institute of Molecular Genetics, Russian Academy of Sciences, and the Zakusov Research Institute of Pharmacology, Russian Academy of Med� ical Sciences, have created the preparation selank, the effective substance of which is a synthetic peptide, an analogue of the short fragment Thr–Lys–Pro–Arg of the heavy chain of human immunoglobulin G, elon� gated at the C terminus with the tripeptide Pro–Gly– Pro. It was shown that selank has a stable nootropic and anxiolytic effects, facilitate brain cell survival in hypoxia, and exhibits an antiviral effect [3, 10].

Molecular identity of a pan cancer marker, CA215

The molecular nature of cancer-associated antigen, CA215 which reacts with RP215 monoclonal antibody and its unique epitope(s) was characterized. RP215 was initially selected and produced from one of 3,000 hybridomas which were generated from mice immunized with the cell extract of OC-3-VGH ovarian cancer cells. This cancer-associated antigen from various sources including cancer cell extract, shed culture medium and affinity-purified forms was analyzed by MALDI-TOF MS (Matrix Adsorption Laser Desorption Ionization-Time of Flight Mass Spectrometry), Western blot, carbohydrate profiling as well as enzyme immunoassays. The results of this study showed that CA215 is homologous to the heavy chains of human immunoglobulins with molecular sizes ranging from 50 to 70 KDa, when probed with RP215 or anti-human immunoglobulin G, A or M. Treatments of cancer cells with NaIO4 drastically reduce RP215 binding to the carbohydrate-associated epitope(s) of CA215 located on the variable domain of the human immunoglobulin heavy chains. Further studies indicated that CA215 is predominantly expressed by cancer cells in both secreted and membrane-bound monomeric forms. The carbohydrate-associated epitope(s) with pH-sensitive immunoactivity appear to be present only in cancer cell-derived immunoglobulins, but not in normal human immunoglobulins. Compared to normal immunoglobulin G, CA215 contains a significantly higher percentage of N-acetyl and N-glycoyl neuraminic acid (28% vs. 8%) in the O-linked glycans, but a lower content of N-acetylglucosamine (28% vs. 41%) in the N-linked ones. It was concluded from this study that RP215 reacts specifically with carbohydrate-associated epitope(s) of immunoglobulin heavy chains expressed by various human cancer cells.

Recombinant full-size human antibody to Ebola virus

A full-size human antibody to Ebola virus was constructed by joining genes encoding the constant domains of the heavy and light chains of human immunoglobulin with the corresponding DNA fragments encoding variable domains of the single-chain antibody 4D1 specific to Ebola virus, which was chosen from a combinatorial phage display library of single-strand human antibodies. Two expression plasmids. pCH1 and pCL1, containing the artificial genes encoding the light and heavy chains of human immunoglobulin, respectively, were constructed. Their cotransfection into the human embryonic kidney cell line HEK293T provided the production of a full-size recombinant human antibody. The affinity constant for the antibody was estimated by solid-phase enzyme-linked immunoassay to be 7.7 x 10(7) +/- 1.5 x 10(7) M(-1). Like the parent single-chain antibody 4DI, the resulting antibody bound the nucleoprotein of Ebola virus and did not interact with the proteins of Marburg virus.

Serum antibodies against Chlamydia pneumoniae outer membrane protein cross-react with the heavy chain of immunoglobulin in the wall of abdominal aortic aneurysms.

Chlamydia pneumoniae (Cp) has been demonstrated in arteries and abdominal aortic aneurysms (AAAs). However, the validity of the methods used is questioned, and antibiotic treatment trials have thus far shown disappointing results. Nevertheless, antibodies against the Cp outer membrane proteins (OMPs) have been associated with progression of atherosclerosis and AAAs. The aim of this study was to detect Cp OMPs in the wall of AAA patients by use of purified serum antibodies directed against Cp OMP and to assess potential cross-reacting proteins in AAA walls. Seventeen patients undergoing infrarenal AAA repair were studied. Full AAA thickness tissue was collected from the anterior wall of the aneurysm. Anti-OMP was extracted from seropositive AAA patients by use of an ELISA kit (Labsystems). Analysis was performed by use of 2D polyacrylamide gel electrophoresis, immunoblotting, and mass spectrometric protein identification. OMP antigens were not detected in 16 of 17 AAA walls. However, 3 major AAA proteins cross-reacted with anti-OMP. The proteins were all identified as heavy chains of human immunoglobulin. We could not find evidence of Cp OMP in 16 of 17 AAA walls, but instead, all samples showed a strong cross-reaction between Cp OMP antibodies and human immunoglobulin. This might indicate that AAA is an autoimmune disease, perhaps triggered by an initial Cp infection.

Rapid capillary gel electrophoresis of proteins

The rapid separation of sodium dodecyl sulphate-protein complexes according to their molecular masses ( M r) by capillary gel electrophoresis is described. Using commercial equipment, standard proteins with M r in the range 29 000–97 400 were resolved to the baseline in less than 2 min by utilizing a separation distance of 7 cm. A linear relationship between migration time and log M r was found and rapid determination of the molecular mass of light and heavy chains of human immunoglobulin G is reported. The results are compared with applications using longer separation distances, showing that rapid and efficient analysis and adequate resolution can be obtained by using short separation distances.

A 41.7 kDa serine protease from Clostridium perfringens type a: Degradation of purified human serum proteins

Two clinical isolates of Clostridium perfringens type A produced a novel caseinolytic serine protease. Both enzymes had a molecular weight of 41.7 kilodaltons and an isoelectric point of 9.1. The two enzymes were immunogenic for rabbits and closely related serologically. Both enzymes partially degraded the heavy chains of human immunoglobulins (Ig) G and IgM, but not IgA. Purified human complement (C) components C3, C5, C8, and C9 were attacked; C1q was refractory. Both enzymes were active against human transferrin, alpha 1-antitrypsin, alpha 2-macroglobulin, haptoglobin, type III fibrinogen, and fibronectin. C-reactive protein was refractory.

Jacalin: a new laboratory tool in immunochemistry and cellular immunology.

In recent years, a new lectin--jacalin--has raised the interest of immunologists because of its original properties with respect to human immunoglobulins and lymphocytes. Its structure and carbohydrate binding specificity are now well documented, and it can be purified easily from jackfruit seeds by ion exchange or affinity chromatography. The binding and precipitating specificities of jacalin with heavy chains of human immunoglobulins allow its use as a diagnostic (IgA subclass typing) and preparative tool (purification of IgA and IgD, removal of IgA from biologic samples and preparations). Other possible applications of jacalin's binding properties also can be envisaged. In addition, the lectin displays a mitogenic activity specific for human CD4 T-lymphocytes; consequently, the proliferative response induced by jacalin appears to represent a new and interesting assay for a functional study of CD4 cells, with obvious applications in primary and acquired, especially AIDS, immune deficiency states.

Inhibition of the classical complement pathway by synthetic peptides from the second constant domain of the heavy chain of human immunoglobulin G.

Inhibition of the classical complement pathway by synthetic peptides from the second constant domain of the heavy chain of human immunoglobulin G.

Interactions of Pseudomonas aeruginosa with immunoglobulins and complement in sputum.

The interactions of Pseudomonas aeruginosa with humoral factors in the sputum of patients with cystic fibrosis were investigated by using an indirect immunofluorescent technique. Fluorescein-conjugated, monovalent antiserum specific to heavy chains of human immunoglobulin A (IgA), IgG, or IgM and to complement C3 were used. All strains of P. aeruginosa recovered from the sputum specimens of patients with cystic fibrosis were found to be coated with antibodies of IgA, IgG, and IgM classes and with C3. The specificity of the antibody coating was determined. The fluorescence was most intense with IgA and was followed in intensity by IgG, IgM, and C3. No difference was noted between rough and mucoid strains of P. aeruginosa. When the subcultured P. aeruginosa was incubated with the sputum eluates, a similar pattern of fluorescence was demonstrated, indicating that these humoral factors are present in the sputum and that the coating process can take place in the lower respiratory tract of the patients. By single radial immunodiffusion, significant quantities of the humoral factors in the sputum eluates were detected. These findings suggest that P. aeruginosa is opsonized in sputum of patients with cystic fibrosis.

Human anaphylatoxin (C3a) from the third component of complement. Primary structure.

C3a anaphylatoxin is derived from the third component (C3) of the blood complement system. Selective proteolysis of C3 by activated proenzymes indigenous to blood generates the C3a fragment. Human C3a was isolated from inulin-activated serum containing 6-aminohexanoic acid, according to recently published procedures (Hugli, T. E., Vallota, E., and Müller-Eberhard, H. J. (1975) J. Biol. Chem. 250, 1472-1498). The human C3a fragment is a highly cationic molecule exhibiting an approximate molecular weight of 9000 and composed of 77 amino acid residues. It consists of a single polypeptide chain containing 8% cysteine and lacks both tryptophan and carbohydrate. A tentative primary structure for the human C3a molecule, deduced from overlapping peptides obtained after cyanogen bromide cleavage, tryptic and chymotryptic digestion, is: See article. Two cystelhylcysteine sequences were established at positions 22, 23 and 56, 57 in human C3a. The 6 half-cystine residues in C3a are all interconnected through three disulfide linkages intersecting in a disulfide knot. The functionally amino acid residues distributed among 14 residues at the COOH-terminal end of C3a. This unusually cationic COOH-terminal region of C3a is presumed to play an important role in the interaction of this protein molecule with cellular receptors. A comparison between the linear sequence of human C3a and the NH2-terminal sequences of light and heavy chains of human immunoglobulin indicates that limited identity exists.

Ultrastructural localization of gamma-chain and immunoglobulin G in human lymphocytes using enzyme-labeled Fab fragment.

By the use of rabbit antibodies against the heavy chain of human immunoglobulin G (IgG), the gamma-chain and IgG molecules were successfully localized at the ultrastructural level in human peripheral lymphocytes. The rabbit Fab fragment was coupled to horseradish peroxidase by means of glutaraldehyde and the resulting conjugate could penetrate the intact plasma membrane. Discernible reaction product was observed in cisternae of the nuclear envelope, rough endoplasmic reticulum and Golgi apparatus as well as on the surface of the lymphocytes. In normal human individuals under no specific antigenic stimulation, only a few peripheral lymphocytes showed a rare positive intractoplasmic reaction. Reaction product may represent either the whole IgG molecule, the half molecule consisting of one heavy and one light chain or nascent gamma-chain.

Amino acid sequences near the “switch point” of heavy chains of human immunoglobulins: Genetic hypothesis

We determined amino acid sequences near the juncture between the variable (V-) and the constant (C-) regions of human immunoglobulin (Ig) α, μ, γ1, γ2 and γ3 chains. Our data show that: (a) the γ1, γ2, and γ3 chains are very similar to one another at the beginning of their C-regions with approximately 90% sequence homology and (b) the α chain has more sequence homology with γ chains (57%) than with μ chains (29%) at the beginning of their C-regions, a finding in contrast to the comparison made by others at the C-termini of H-chains where α chain was found to be more homologous to μ than to γ chain. Comparison of our data with amino acid sequences of human γ1 and μ chains published to date shows that: (a) the “switch point” between the V- and C-regions of human Ig H-chains is most likely between positions 117 and 118 (Eu numbering), and (b) several residues at the end of the V-regions are either invariable or nearly invariable. A model is presented as a possible explanation for their significance in the joining of the V-and C-regions.

Variation and homology in the mu and gamma heavy chains of human immunoglobulins.

Sequence analysis of an 1gM immunoglobulin shows that the variable regions of hunman micro and gamma1 heavy chainis may have twice as much homology as their constant regions and that evolutionary divergence of micro and gamma1 heavy chain genes occurred not long after the separation of heavy and light chain genes.

The amino-terminal sequence of the heavy chain of human immunoglobulin M.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe amino-terminal sequence of the heavy chain of human immunoglobulin MJ. Claude. BennettCite this: Biochemistry 1968, 7, 10, 3340–3344Publication Date (Print):October 1, 1968Publication History Published online1 May 2002Published inissue 1 October 1968https://doi.org/10.1021/bi00850a005RIGHTS & PERMISSIONSArticle Views33Altmetric-Citations32LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (455 KB) Get e-Alerts Get e-Alerts

The C-terminal sequences of the heavy chains of human immunoglobulin G myeloma proteins of differing isotopes and allotypes

The sequences of the C-terminal octadecapeptides obtained by cyanogen bromide cleavage of the gamma-chains of myeloma proteins of the four subclasses, and a urinary heavy-chain-disease protein, have been determined. Although the sequences were markedly homologous, unique replacements were identified that distinguished between the gamma(2b), gamma(2c) and gamma(2d) subclasses. The data are in accord with the postulated existence of four genetic loci or cistrons, these having arisen by the process of gene duplication.

Distribution of an arginine-lysine interchange in the invariable half of human L-type Bence-Jones proteins.

SEROLOGICAL reagents have been used to identify allelic antigenic determinants of the peptide chains of immunoglobulins1. Several allotypic determinants of the heavy chains of human immunoglobulins have been identified2 and their distribution in human populations3 has been investigated. Only a few allotypic determinants of the K-type light chain of human immunoglobulins have been identified2 and one of these has been correlated with an amino-acid interchange in the invariable half of these peptide chains4–6. No homologous serological reagent has been available for the study of the L-type light chain.