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.

Chemical structure of light chains: amino acid sequence of type K Bence-Jones proteins

1966 ◽  
Vol 166 (1003) ◽  
pp. 124-137 ◽  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Sequence Data ◽  
Single Point ◽  
Structural Difference ◽  
Light Chains ◽  
Single Point Mutation ◽  
Amino Terminal ◽  
Type K ◽  
Bence Jones Proteins

Bence-Jones proteins are the light chains of the autologous myeloma globulin and are analogous to the light chains of normal human immunoglobulins. Peptide mapping has demonstrated that Bence-Jones proteins share a fixed portion of their sequence (the ‘constant’ portion) and also have a mutable part (the ‘variable’ portion). Sequence analysis and ordering of the tryptic and chymotryptic peptides has provided the tentative complete amino acid sequence of one Bence-Jones protein of antigenic type K. Comparison with partial sequence data for other type K Bence-Jones proteins has revealed many structural differences in the amino terminal half of the molecules, but only one structural difference in the carboxyl terminal half. The latter is strongly correlated with the Inv genetic factor. The points of interchange in the amino terminal half occur in clusters close to the half cystine residues and the ‘switch peptide’ (positions 102 through 105), after which the sequence becomes essentially invariant. This suggests that the major areas subject to sequence variation are part of a single topographical region which may define a portion of the antigen combining site in the light chains of antibodies. Many, but not all, the amino acid interchanges are compatible with a single point mutation. As yet, no single mutational theory suffices to explain the manifold differences in structure of the light chains. Such structural variation, however, could result from the presence of many related genes.

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.

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 Complete amino acid sequences of variable regions of two human IgM rheumatoid factors, BOR and KAS of the Wa idiotypic family, reveal restricted use of heavy and light chain variable and joining region gene segments.

1987 ◽  
Vol 166 (2) ◽  
pp. 550-564 ◽  
Author(s):  
M M Newkirk ◽  
R A Mageed ◽  
R Jefferis ◽  
P P Chen ◽  
J D Capra
Keyword(s):  
Amino Acid ◽  
Gene Segment ◽  
Variable Region ◽  
Amino Acid Sequences ◽  
Light Chains ◽  
Rheumatoid Factors ◽  
Region Gene ◽  
Variable Regions ◽  
D Region ◽  
Restricted Use

Evidence derived from the complete amino acid sequences of the variable regions of both the heavy and light chains of two members (BOR and KAS) of the Wa idiotypic family of human rheumatoid factors suggests that not only are the light chains of these molecules derived from possibly one variable region gene segment, but the heavy chain variable regions are all derived from the VHI subgroup of human V region genes. These molecules exhibit a surprising conservation in the size of D region, and all use the JH4 gene element. This restriction in use of VL, VH, D, and JH suggests all of these elements may play a crucial role in either antigen binding and/or expression of the crossreactive idiotype.

Genetic control of immunoglobulin synthesis

1970 ◽  
Vol 176 (1044) ◽  
pp. 329-346 ◽  
Keyword(s):  
Genetic Control ◽  
Mammalian Species ◽  
Variable Region ◽  
Lymphoid Cells ◽  
The Other ◽  
Light Chains ◽  
Common Region ◽  
Variable Regions ◽  
Immunoglobulin Synthesis ◽  
Heavy Chains

The structural features of immunoglobulins are described. This family of related proteins shows a common structural design: two identical light chains and two identical heavy chains are present in each molecule. Amino acid sequence studies have shown that light chains have one of two types of sequences in the C terminal half, whereas they differ one from the other in the N terminal half. The two halves of the sequence have been designated accordingly variable and common half. Similarly, the heavy chains have a common sequence in the C terminal three-quarters of the sequence and a variable one in the N terminal quarter. Genetic studies on the inheritance of immunoglobulin alleles have been carried out in some mammalian species. The genetic control of immunoglobulin synthesis is reviewed in man, mouse and rabbit. These studies have shown that each allele controls the inheritance of a specific common region, with the exception of one genetic system which seems to control the synthesis of the variable region of rabbit heavy chains. Immunoglobulin chains are clearly synthesized under the control of two distinct genetic elements, one of which specifies the variable region and the other the common region. The possible significance of this type of genetic control of immunoglobulin structure is discussed. It has not yet been established whether each variant of the variable region is coded for by an individual structural gene present in the genome of each individual or whether few genes for variable regions exist, which in the course of the differentiation of lymphoid cells are subject to somatic mutation processes, which generate variability. These two possibilities are discussed and elements in favour of one or the other theory are presented.

scholarly journals Sequence similarities among kappa IIIb chains of monoclonal human IgM kappa autoantibodies.

1984 ◽  
Vol 160 (3) ◽  
pp. 893-904 ◽  
Author(s):  
B Pons-Estel ◽  
F Goñi ◽  
A Solomon ◽  
B Frangione
Keyword(s):  
Amino Acid ◽  
Germ Line ◽  
Sequence Data ◽  
Selection Process ◽  
Variable Region ◽  
Light Chains ◽  
Partial Amino Acid Sequence ◽  
Kappa Chain ◽  
V Region ◽  
Sequence Similarities

Light chains of the serologically and chemically defined V region sub-subgroup kappa IIIb are preferentially associated with several types of human IgM kappa (monoclonal) autoantibodies and are remarkably homologous in primary structure, as evidenced by partial amino acid sequence data. To establish the extent of homology among such proteins, we have determined the complete variable region (V) sequence of the light chains of four monoclonal IgM kappa autoantibodies, of which two (GAR and GOT) are rheumatoid factors (RFs), the third (SON) has anti-apo beta lipoprotein specificity, and the fourth (PIE) binds specifically to intermediate filaments. The region encoded by the V kappa segment gene (positions 1-95) in all four light (L) chains is virtually identical in sequence, differing by only one residue in the FR3 of protein SON and in the first CDR of protein GOT. Further, the CDR3 of kappa chain SON contains an additional residue (prolyl) located at the carboxyl-terminus of the V segment. The region encoded by the J gene (positions 96-108) is identical after position 96 for the two RFs GAR and GOT (J kappa 2), but different in proteins SON (J kappa 4) and PIE (J kappa 1). The amino acid residue at position 96, located in CDR3 at the site of combinatoriaL joining of the V kappa and J kappa gene segments and involved as a contacting residue in the hapten binding site, is different in all four light chains. These results demonstrate the extensive homology in sequence among light chains of IgM kappa autoantibodies and indicate that a particular V kappa germ line gene, kappa IIIb, is expressed as a phylogenetic response to certain self antigens or as part of a selection process by which these autoimmune responses are regulated.

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.

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