scholarly journals The specificity of chain interactions among immunoglobulins. Combinations of γ chains with κ chains of the same subgroup as in the parent immunoglobulin G

1974 ◽  
Vol 139 (2) ◽  
pp. 369-374 ◽  
Author(s):  
G. T. Stevenson ◽  
L. E. Mole
Keyword(s):  
Immunoglobulin G ◽  
Structural Information ◽  
Variable Region ◽  
Light Chains ◽  
Predominant Role ◽  
Variable Regions ◽  
Human Immunoglobulins ◽  
Myeloma Proteins ◽  
Standard Population ◽  
Normal Light

1. The specificity of combination of heavy and light chains from selected human immunoglobulins was examined in the light of greater structural information than in previous studies. Heavy (γ) chains from immunoglobulin G (κ) myeloma proteins were allowed to combine with their homologous light (κ) chains or with other κ chains of the same variable-region subgroup. The affinity of each such pairing was assessed by having the test κ chain compete with a standard population of normal light chains. 2. There was a spread of affinities among the heavy–light pairings with the homologous pairings having an average affinity significantly higher than the heterologous pairings. 3. It follows that (a) the preference shown for homologous heavy–light pairings is not explicable simply in terms of the known subdivisions of the variable and constant regions of the chains, and (b) it is unlikely that those residues specifying the subgroups of κ-chain variable regions have a predominant role in the formation of interchain bonds with the γ-chain variable regions.

scholarly journals A major group of mouse kappa chains controlled by the chromosome 6 locus, IgK-Ef2.

1980 ◽  
Vol 152 (3) ◽  
pp. 555-564 ◽  
Author(s):  
C Lazure ◽  
W T Hum ◽  
D M Gibson
Keyword(s):  
Light Chain ◽  
Normal Mouse ◽  
Variable Region ◽  
Normal Serum ◽  
Light Chains ◽  
Mouse Serum ◽  
Chromosome 6 ◽  
Frequency Of Occurrence ◽  
Myeloma Proteins ◽  
Normal Light

We previously demonstrated that loci closely linked to the Ly-3 locus control the expression of distinct sets of light chains in normal mouse serum immunoglobulin. One of these loci, IgK-Ef2, was shown to control two major bands in normal light chain isoelectric focusing (IF) profiles. Strains possessing the marker bands were designated IgK-Ef2a. Screening of myeloma proteins from the strains BALB/c (IgK-Ef2a) and NZB (IgK-Ef2b) led to the identification of eight proteins in the BALB/c collection having light chains that cofocus precisely with the polymorphic IF bands observed in normal serum light chains. Partial sequence analysis of 3 of the light chains has shown that they are all identical in the first 30 positions, which indicates that they constitute a single variable region of the kappa light chain (VK) group (VK1). The frequency of occurrence of the group within the BALB/c myeloma collections (8 out of 277) suggests that the number of such groups may be closer to 50 than to 100. The finding supports an interpretation of the genetic polymorphism as being in part a result of the absence of genes related to VK1 in IgK-Ef2b strains of mice.

Homology and Relatedness of Amino Acid Interchanges in the Variable Region of κ Light Chains from Human Immunoglobulins

1972 ◽  
Vol 50 (10) ◽  
pp. 1122-1131 ◽  
Author(s):  
M. E. Percy ◽  
J. R. Percy
Keyword(s):  
Amino Acid ◽  
Variable Region ◽  
Light Chains ◽  
Variable Regions ◽  
Amino Terminal ◽  
Functional Homology ◽  
Hypervariable Regions ◽  
Human Immunoglobulins ◽  
Polypeptide Chains ◽  
High Degree

We have devised a method for assessing the relatedness of amino acid interchanges in the variable regions of immunoglobulin polypeptide chains, in terms of the nature of the differences between trinucleotide codons. We have used it to construct a map of the average human κ chain showing the positions which (i) give the chain κ identity, (ii) give the chain subgroup identity within the κ type, (iii) give the chain identity within a subgroup, and (iv) are invariant. In order to determine the positions at which the interchanges are homologous, we have performed a second analysis using the assumption that functionally equivalent amino acids are identical.κ Identity was found throughout the amino-terminal half of the chain (positions 1–108, the variable region). Subgroup identity was not found beyond invariant Phe 98, but was very pronounced in the first 22 positions of the chain. κ and subgroup identity were evident within hypervariable regions (positions 27–35, 48–52, and 90–97), however. A high degree of functional homology was found in the 11 residues at the end of the variable region and at certain individual positions scattered throughout the variable region, but not in the hypervariable regions.The distribution of these different classes of positions might reflect the distribution of certain functions within the chains.

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 Glycopeptides from human χ-chains

1971 ◽  
Vol 121 (2) ◽  
pp. 211-215 ◽  
Author(s):  
Celia P. Milstein ◽  
C. Milstein
Keyword(s):  
Attachment Site ◽  
Variable Region ◽  
Light Chains ◽  
Myeloma Proteins

Glycopeptides have been isolated from tryptic digests of κ-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, κI type, is derived from position 25–31 whereas that from Rai, κII 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.

scholarly journals AN ANALYSIS OF THE SEQUENCES OF THE VARIABLE REGIONS OF BENCE JONES PROTEINS AND MYELOMA LIGHT CHAINS AND THEIR IMPLICATIONS FOR ANTIBODY COMPLEMENTARITY

1970 ◽  
Vol 132 (2) ◽  
pp. 211-250 ◽  
Author(s):  
Tai Te Wu ◽  
Elvin A. Kabat
Keyword(s):  
Sequence Data ◽  
Variable Region ◽  
High Variability ◽  
Light Chains ◽  
Variable Regions ◽  
Advantages And Disadvantages ◽  
Specific Subgroup ◽  
Species Specific ◽  
Specific Species ◽  
Bence Jones Proteins

In an attempt to account for antibody specificity and complementarity in terms of structure, human κ-, human λ-, and mouse κ-Bence Jones proteins and light chains are considered as a single population and the variable and constant regions are compared using the sequence data available. Statistical criteria are used in evaluating each position in the sequence as to whether it is essentially invariant or group-specific, subgroup-specific, species-specific, etc. Examination of the invariant residues of the variable and constant regions confirms the existence of a large number of invariant glycines, no invariant valine, lysine, and histidine, and only one invariant leucine and alanine in the variable region, as compared with the absence of invariant glycines and presence of three each of invariant alanine, leucine, and valine and two each of invariant lysine and histidine in the constant region. The unique role of glycine in the variable region is emphasized. Hydrophobicity of the invariant residues of the two regions is also evaluated. A parameter termed variability is defined and plotted against the position for the 107 residues of the variable region. Three stretches of unusually high variability are noted at residues 24–34, 50–56, and 89–97; variations in length have been found in the first and third of these. It is hypothesized that positions 24–34 and 89–97 contain the complementarity-determining residues of the light chain—those which make contact with the antigenic determinant. The heavy chain also has been reported to have a similar region of very high variability which would also participate in forming the antibody-combining site. It is postulated that the information for site complementarity is contained in some extrachromosomal DNA such as an episome and is incorporated by insertion into the DNA of the structural genes for the variable region of short linear sequences of nucleotides. The advantages and disadvantages of this hypothesis are discussed.

scholarly journals The amino acid sequences of the Fd fragments of two human γ 1 heavy chains

1970 ◽  
Vol 117 (4) ◽  
pp. 641-660 ◽  
Author(s):  
E. M. Press ◽  
N. M. Hogg
Keyword(s):  
Amino Acid ◽  
Aspartic Acid ◽  
Heavy Chain ◽  
Variable Region ◽  
Amino Acid Sequences ◽  
Light Chains ◽  
Aspartic Acid Residue ◽  
Variable Regions ◽  
Heavy Chain Variable Region ◽  
Heavy Chains

The amino acid sequences of the Fd fragments of two human pathological immunoglobulins of the immunoglobulin G1 class are reported. Comparison of the two sequences shows that the heavy-chain variable regions are similar in length to those of the light chains. The existence of heavy chain variable region subgroups is also deduced, from a comparison of these two sequences with those of another γ 1 chain, Eu, a μ chain, Ou, and the partial sequence of a fourth γ 1 chain, Ste. Carbohydrate has been found to be linked to an aspartic acid residue in the variable region of one of the γ 1 chains, Cor.

Immunoglobulin Diversity: Correlation of Non-Allelic Antigenic Markers with the Basic Sequences of the Variable Region of Human Lambda Chains

1976 ◽  
Vol 31 (11-12) ◽  
pp. 758-760 ◽  
Author(s):  
F. W. Tisdiendorf ◽  
M. M. Tischendorf ◽  
B. Wittmann-Liebold
Keyword(s):  
Variable Region ◽  
Light Chains ◽  
Sequence Determination ◽  
Amino Terminal ◽  
Genes Encoding ◽  
V Region ◽  
Normal Light ◽  
Bence Jones Proteins

Three forms of the amino terminal half (variable region) of human pathological lambda light chains of immunoglobulins were identified antigenically. By study of all completely sequenced Bence Jones proteins hitherto analyzed and a greater number of proteins subjected to automated sequence determination as well as normal light chains three distinct isotypic basic sequences were identified. The basic sequences are shown to be associated with characteristic antigenic markers representing three V region genes encoding the variable half of lambda chains of immunoglobulins.

scholarly journals Sequence of a cDNA encoding Basilea kappa light chains (K2 isotype) suggests a possible relationship of protein structure to limited expression.

1984 ◽  
Vol 159 (2) ◽  
pp. 635-640 ◽  
Author(s):  
K E Bernstein ◽  
E Lamoyi ◽  
N McCartney-Francis ◽  
R G Mage
Keyword(s):  
Sulfhydryl Group ◽  
Variable Region ◽  
Complete Sequence ◽  
Light Chains ◽  
Small Subset ◽  
Constant Region ◽  
Region Gene ◽  
Variable Regions ◽  
Immunoglobulin Kappa ◽  
Kappa Light Chains

We present the complete sequence of a cDNA encoding rabbit immunoglobulin kappa light chains of the Basilea isotype (K2). Although all rabbits seem to possess a K2 constant region gene, expression of this gene in most rabbits is minimal if present at all. Even in Basilea rabbits the majority of expressed immunoglobulins are of lambda type. We find that the sequence of our Basilea cDNA constant region and the sequence of a "silent" K2 gene from b4 rabbits (bas-N4) are almost identical. The bas (K2) isotype lacks cysteine at position 171 in the constant region that is present in all K1 constant regions and usually forms an interdomain disulfide bond, with a cysteine at position 80 of the variable region. We postulate that one factor contributing to the low expression of the bas (K2) isotype could be a paucity of V kappa regions lacking cysteine at position 80. If a typical rabbit V kappa encoding Cys at position 80 is rearranged and expressed with th K2 isotype. B cells with mRNAs encoding light chains with free sulfhydryl groups would result. These cells may fail to form functional immunoglobulin receptors. Only a small subset of rabbit variable regions that lack the cysteine at position 80 would rearrange and encode K2 light chains lacking a free sulfhydryl group.

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