scholarly journals Intrachain disulphide bridges in immunoglobulin G heavy chains. The Fc fragment

1968 ◽  
Vol 106 (1) ◽  
pp. 15-21 ◽  
Author(s):  
B. Frangione ◽  
C. Milstein ◽  
Edward C. Franklin
Keyword(s):  
Heavy Chain ◽  
Immunoglobulin G ◽  
The Other ◽  
Light Chains ◽  
Fc Fragment ◽  
Heavy Chains ◽  
Human Immunoglobulins ◽  
Other Hand ◽  
Terminal Loop ◽  
Heavy Chain Disease

The disulphide bridges of the Fc fragment (C-terminal half of the heavy chain) have been studied in several human immunoglobulins, containing heavy chains of different antigenic types (γ1, γ2, γ3 and γ4), and in heavy-chain-disease proteins. Two intrachain disulphide bridges were found to be present. The sequences appear to be identical in the Fc fragments of two types of chain studied (γ1 and γ3), and very similar to corresponding sequences of the Fc fragment in rabbit. These results suggest that the C-terminal half of the heavy chains is covalently folded (in a similar fashion to the light chains) with a C-terminal loop and an N-terminal loop. The similarity is emphasized by comparison of the sequence and location of the disulphide-bridged peptides of the C-terminal loop of heavy and light chains. The N-terminal loop, on the other hand, appears to be very different in Fc fragments and light chains. The C-terminal loop is the only one present in the F′c fragment.

scholarly journals Goat immunoglobin G. Peptide chains and terminal residues

1969 ◽  
Vol 115 (3) ◽  
pp. 371-375 ◽  
Author(s):  
D. Givol ◽  
E. Hurwitz
Keyword(s):  
Carboxylic Acid ◽  
Heavy Chain ◽  
Light Chain ◽  
Immunoglobulin G ◽  
Light Chains ◽  
Terminal Sequence ◽  
Terminal Residue ◽  
Heavy Chains ◽  
Molecular Weights ◽  
Immunoglobin G

Goat immunoglobulin G (IgG) was isolated and characterized. The molecular weights of the IgG and its heavy chains and light chains were found to be 144000, 53600 and 23000 respectively. The light chain corresponds to human L type as was shown by the absence of C-terminal S-carboxymethylcysteine and its high content of N-terminal pyrrolid-2-one-5-carboxylic acid (PCA). The major C-terminal residue of the light chain was serine and the major N-terminal dipeptide was PCA-Ala (0·6mole/mole). The major C-terminal residue of the heavy chain was glycine and the N-terminal sequence of the heavy chain is PCA-Val-Gln. This tripeptide was obtained in a 70% yield.

Studies on the amino acid sequence of heavy chains from rabbit immunoglobulin G

1966 ◽  
Vol 166 (1003) ◽  
pp. 159-175 ◽  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Heavy Chain ◽  
Immunoglobulin G ◽  
Light Chains ◽  
Antibody Specificity ◽  
Sequence Heterogeneity ◽  
Specific Antibodies ◽  
Heavy Chains ◽  
Insight Into

It is now generally agreed that the four-chain subunit structure of Immunoglobulins which was first proposed by Porter (1962), accurately represents the gross structure of immunoglobulin G (IgG) and specific antibodies (Fleischman, Porter & Press 1963; Edelman & Gally 1964; Marler, Nelson & Tanford 1964; Nelson et al . 1965). However, an understanding of the structural basis of antibody specificity requires greater insight into the amino acid sequence of the polypeptide chain components of specific antibodies. Isolated light chains from specific antibodies and inert IgG, show a considerable degree of electrophoretic heterogeneity (Edelman & Gally 1964; Cohen & Porter 1964; Poulik 1964). Tryptic peptide maps of light chains (Nelson et al . 1965) have suggested that this heterogeneity may be accounted for by differences in amino acid sequence. This view has received considerable support from the observation that Bence-Jones proteins, which may be regarded as light chains, vary significantly in amino acid sequence (Hilschman & Craig 1965; Milstein 1966; Titani, Whitley & Putman 1966). A similar but less well-defined sequence heterogeneity has been suggested to exist in the heavy chains of specific antibodies (Feinstein 1964). However, the Fc fragment of the heavy chains has been thought to possess a regular amino acid sequence which may be similar, if not identical, among all specific antibodies (Porter 1959; Nelson et al . 1965). This paper summarizes the results of studies on the amino acid sequence of heavy chains and that portion of heavy chain, Fc fragment, which is obtained on treatment of rabbit IgG with papain (Porter 1959). These studies were designed to determine how much of the amino acid sequence of heavy chain could be accounted for by a unique, regular amino acid sequence which was common to most, if not all, IgG antibodies. In addition, attempts were made to locate regions of heavy chains which varied in amino acid sequence. Although structural variants appear to occur among the heavy chains found in non-specific IgG, it would be desirable to know what portion of the heavy chain sequence is invariant among all antibodies. If antibody specificity results from sequence heterogeneity in light and heavy chains, then knowledge of the variant and invariant portions of these chains may provide insight into the nature of specific binding sites in anti-­bodies.

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

1967 ◽  
Vol 105 (3) ◽  
pp. 1019-1028 ◽  
Author(s):  
J. W. Prahl
Keyword(s):  
Gene Duplication ◽  
Heavy Chain ◽  
Immunoglobulin G ◽  
Cyanogen Bromide ◽  
Human Immunoglobulin ◽  
Human Immunoglobulin G ◽  
Heavy Chains ◽  
Myeloma Proteins ◽  
Disease Protein ◽  
Heavy Chain Disease

The sequences of the C-terminal octadecapeptides obtained by cyanogen bromide cleavage of the γ-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 γ2b, γ2c and γ2d 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.

Rocket Immunoselection for Detection of Heavy-Chain Diseases

1974 ◽  
Vol 20 (10) ◽  
pp. 1292-1294 ◽  
Author(s):  
D S J Gale ◽  
J M B Versey ◽  
John R Hobbs
Keyword(s):  
Heavy Chain ◽  
Light Chains ◽  
Lower Section ◽  
Lower Region ◽  
Heavy Chains ◽  
Heavy Chain Diseases ◽  
Heavy Chain Disease

Abstract A method is described that allows heavy-chain disease proteins to be simply detected. The sample is electrophoresed in an agarose plate containing kappa and lambda antisera in the lower section, and the relevant heavy-chain antisera in the upper section. Light chains and immunoglobulins containing light chains are precipitated in the lower region. Free "heavy chains" migrate into the upper region, where they are precipitated as a separate rocket. The method is quick, sensitive, and requires little antiserum.

scholarly journals STRUCTURAL STUDIES OF HUMAN γG-MYELOMA PROTEINS OF DIFFERENT ANTIGENIC SUBGROUPS AND GENETIC SPECIFICITIES

1966 ◽  
Vol 124 (4) ◽  
pp. 715-732 ◽  
Author(s):  
B. Frangione ◽  
E. C. Franklin ◽  
H. H. Fudenberg ◽  
M. E. Koshland
Keyword(s):  
Amino Acids ◽  
Glutamic Acid ◽  
Heavy Chain ◽  
The Other ◽  
Structural Studies ◽  
Heavy Chains ◽  
Myeloma Proteins ◽  
Methionine Sulfone ◽  
Peptide Maps ◽  
Heavy Chain Disease

1. Peptide maps of Fc fragments or heavy chains of 36 G myeloma proteins and two "heavy chain disease" proteins belonging to the four γ-chain subgroups revealed very striking similarities between them. However differences in a few peptides were noted. This was most pronounced for the Ge(γ2d) 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(γ2b) proteins had a peptide previously shown to be characteristic of normal Gm(a+) γG-globulins. Fc fragments from Gm(a-) molecules belonging to the We(γ2b), Vi(γ2c), or Ne(γ2a) subgroups, whether Gm(b+), Gm(f+), or Gm(-), had the peptide previously identified in Gm(b+f+) normal γG-globulin. This "non-a" peptide was absent in peptide maps from Gm(-) molecules of the Ge(γ2d) 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.

scholarly journals SIX BALB/c IgA MYELOMA PROTEINS THAT BIND ß-(1 → 6)-D-GALACTAN

1973 ◽  
Vol 138 (5) ◽  
pp. 1095-1106 ◽  
Author(s):  
Stuart Rudikoff ◽  
Elizabeth B. Mushinski ◽  
Michael Potter ◽  
C. P. J. Glaudemans ◽  
Michael E. Jolley
Keyword(s):  
Amino Acid ◽  
Affinity Chromatography ◽  
Heavy Chain ◽  
Antigenic Determinant ◽  
Amino Acid Sequences ◽  
The Other ◽  
Light Chains ◽  
Heavy Chains ◽  
Myeloma Proteins ◽  
Highly Sensitive

Six IgA myeloma proteins of BALB/c origin which bind antigens containing ß-(1 → 6)-D-galactan side chains have been isolated by affinity chromatography on galactoside-BSA-Sepharose columns. Partial amino acid sequences of of the light chains to residue Cys23 and the heavy chains to reside 30 were determined on the automated sequencer. No differences were found among the six VK sequences. Among some 50 partial VK sequences that have thus far been determined these six chains are the only ones thus far identified in this subgroup; at least 25 VK subgroups in the mouse have been identified so far. The heavy chain partial sequences were also very closely related but two differences were found. One protein differed from the other five by having isoleucine instead of leucine at position 5, a second protein differed from the others by having an unidentified amino acid at position 19. Using the highly sensitive inhibition of hemagglutination method it was found that each of the proteins possessed a unique inidividual antigenic determinant.

scholarly journals Gamma heavy chain disease complicated by pulmonary hypertension, which was successfully treated with lenalidomide

2020 ◽  
Vol 13 (11) ◽  
pp. e236162
Author(s):  
Sho Shibata ◽  
Akiko Fukunaga
Keyword(s):  
Pulmonary Hypertension ◽  
Heavy Chain ◽  
Elevated Level ◽  
Lower Leg ◽  
Light Chains ◽  
Monoclonal Immunoglobulin ◽  
Heavy Chains ◽  
First Case ◽  
Dexamethasone Therapy ◽  
Heavy Chain Disease

Heavy chain disease (HCD) is a rare B-cell proliferative neoplasm that is characterised by the production of truncated monoclonal immunoglobulin heavy chains without light chains. Gamma HCD is a subgroup of HCD. A 67-year-old man was admitted to our hospital with dyspnoea and lower leg oedema. Based on the results of heart catheterisation, he was diagnosed with pulmonary hypertension. Laboratory tests revealed an elevated level of IgG, and serum immunoelectrophoresis showed that IgG was a monoclonal gamma heavy chain without light chains. Finally, he was diagnosed with gamma HCD complicated by pulmonary hypertension. Bortezomib and dexamethasone therapy was initiated, but became refractory within 8 months. Therefore, the treatment was switched to lenalidomide and dexamethasone therapy, and the disease has been stably controlled for more than 2 years. To the best of our knowledge, this is the first case of gamma HCD being successfully treated by lenalidomide and dexamethasone therapy.

scholarly journals Amino acid sequence of the N-terminal sixty-nine residues of heavy chain derived from a homogeneous rabbit antibody

1972 ◽  
Vol 130 (2) ◽  
pp. 539-546 ◽  
Author(s):  
Jean-Claude Jaton ◽  
D. G. Braun
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Heavy Chain ◽  
Sequence Variation ◽  
Sequence Variability ◽  
Rabbit Antibody ◽  
Heavy Chains ◽  
Human Immunoglobulins ◽  
Variable Section ◽  
Chain Sequence

The sequence of the N-terminal 69 residues of heavy chain from a homogeneous rabbit antibody to type III pneumococcal polysaccharide was determined. The sequence is similar to that found in heavy chains of normal pooled rabbit immunoglobulins of the same allotype Aa1. Two regions of the homogeneous heavy chain (residues 35–46 and 62–69) are very similar to corresponding regions of heavy chains from rabbit Aa2 immunoglobulin, as well as from mouse, guinea-pig and human immunoglobulins. In contrast, residues 47–62 appear to be variable. Comparison in this section with another homogeneous anti-pneumococcal antibody (Strosberg et al., 1972) of related specificity and of the same allotype indicates sequence variation in at least three positions. An antibody to group C streptococcal carbohydrate of allotype Aa2 (Fleischman, 1971) differs by five amino acids in the same region of the heavy chain. Sequence variability between these three antibodies does not occur in homologous positions within this variable section. Allotype-related sequences could not be identified in section 34–65.

scholarly journals Affinity labelling of the binding site of rabbit antibody. Evidence for the involvement of the hypervariable regions of the heavy chain

1974 ◽  
Vol 139 (1) ◽  
pp. 135-149 ◽  
Author(s):  
Christopher E. Fisher ◽  
Elizabeth M. Press
Keyword(s):  
Binding Site ◽  
Heavy Chain ◽  
Binding Sites ◽  
Light Chains ◽  
Rabbit Antibody ◽  
Heavy Chains ◽  
Group 4 ◽  
Hypervariable Regions ◽  
Affinity Labelling ◽  
Antibody Complex

The binding sites of rabbit antibodies with affinity for the haptenic group 4-azido-2-nitrophenyl-lysine have been specifically labelled by photolysis of the hapten–antibody complex. The extent of covalent labelling was 0.5–0.9mol of hapten bound/mol of antibody and, by using an immunoadsorbent, antibody with 1.3mol of hapten/mol was obtained. The antibody was specifically labelled in the binding site and the ratio of labelling of heavy and light chains was in the range 3.3–5.0. The labelled heavy chains were cleaved by CNBr treatment and after reduction and alkylation of the intrachain bonds, were digested with trypsin. Evidence is presented that two regions of the heavy chain, positions 29–34 and 95–114, together contain about 80% of the label on the heavy chain; these two regions respectively include two of the hypervariable regions of rabbit heavy chain.

A 59-Year-Old Woman With Immunotactoid Glomerulopathy, Heavy-Chain Disease, and Non-Hodgkin Lymphoma

2004 ◽  
Vol 128 (6) ◽  
pp. 689-692
Author(s):  
Erica Jacobson ◽  
Gregory Sharp ◽  
Jeffrey Rimmer ◽  
Bruce MacPherson
Keyword(s):  
Hodgkin Lymphoma ◽  
Heavy Chain ◽  
Average Diameter ◽  
World Health ◽  
Heavy Chains ◽  
Non Hodgkin Lymphoma ◽  
Immunotactoid Glomerulopathy ◽  
History Of ◽  
Health Organization ◽  
Heavy Chain Disease

Abstract Immunotactoid glomerulopathy is one of several renal disorders characterized by the extracellular deposition of nonamyloid fibrillary deposits. There is considerable debate as to whether immunotactoid glomerulopathy should be distinguished from fibrillary glomerulonephritis, a closely related entity. Currently, the distinction is based on fibril size and arrangement. We report the case of a 59-year-old woman in whom a diagnosis of immunotactoid glomerulopathy was made after a 2-year history of proteinuria. Electron microscopy of her renal biopsy showed randomly arranged microtubular subepithelial and mesangial deposits, which measured 34 nm in average diameter. She was later discovered to have circulating immunoglobulin G heavy chains without associated light chains (γ-heavy-chain disease) and, subsequently, non-Hodgkin lymphoma, follicular lymphoma, grade I (World Health Organization classification). Approximately 100 cases of γ-heavy-chain disease have been reported in the literature since it was originally described by Franklin in 1964. However, while there are 10 reports in the literature of heavy-chain disease with fibrillary deposits in the kidney, none fit the criteria for immunotactoid glomerulopathy.

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