Subgroups of Amino Acid Sequences in the Variable Regions of Immunoglobulin Heavy Chains

Cunningham, Bruce A.; Pflumm, Mollie N.; User, Urs Rutisha; Edelman, Gerald M.

doi:10.1073/pnas.64.3.997

Cited by 73 publications

(11 citation statements)

References 19 publications

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“…Another subgroup is based on similarity to the variable sequence of the yl heavy chain Eu. This second kind Cunningham et al (8) refer to as subgroup I and the kind first discovered as subgroup II. We have extensive sequence data on ju chains that show that both of these subgroups are found in yM immunoglobulins, and we have discovered a third subgroup that differs from the first two in having a free NH2terminal residue of glutamic acid and its own characteristic variable region sequence (20,21).…”

mentioning

confidence: 95%

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Macroglobulin Structure: Variable Sequence of Light and Heavy Chains

Köhler

Shimizu

Paul

et al. 1970

Science

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mentioning

confidence: 95%

“…Whereas the K and A variable regions are characteristic of the antigenic class of light chain, the variable region of it and y chains appears to be independent of the class of heavy chain (4,(7)(8)(9).…”

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confidence: 99%

Macroglobulin Structure: Variable Sequence of Light and Heavy Chains

Köhler

Shimizu

Paul

et al. 1970

Science

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“…Thus there are about 8 (human K and mouse K) to 10 (human X) glycines in the variable region of the light chains of all proteins for which sequence data are available at these positions. They are as follows: (56,57) shows Gly-Gln-Gly at positions 112, 113, and 114 in two instances (He and Daw), Gly-Arg-Gly in one (Cor) and Gly-Gly at positions 114 and 115 in Eu; but in the latter protein two gaps have been placed at positions 108 and 109 in aligning with He for maximum homology. Thus these glycines could also be functionally and positionally equivalent.…”

mentioning

confidence: 99%

An Analysis of the Sequences of the Variable Regions of Bence Jones Proteins and Myeloma Light Chains and Their Implications for Antibody Complementarity

Kabat

1970

The Journal of Experimental Medicine

1,256

461

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The extraordinary versatility of the antibody-forming mechanism in producing an almost limitless number of specific receptor sites complementary for almost any molecular conformation of matter within a size range (1-3) represented by a hexa-or heptasaccharide as an upper and a mono-or disaccharide as a lower limit, is almost certainly related to the unique structural features of immunoglobulins and differentiates them from all other known proteins. These antibody-combining sites are formed as a consequence of the interaction of two polypeptide chains, a light and a heavy chain (2, 4, 5). The antibodies usually formed to various antigens often represent heterogeneous populations of immunoglobulin molecules of different classes, subclasses, and genetic variants and also show specificities tgward different antigenic determinants (1, 2, 6, 7). In some instances, however, relatively homogeneous populations of antibodies with respect to many of these properties have been obtained. Among these have been human antibodies to dextran and levan (8, 9) and rabbit antibodies to the group-specific carbohydrate of streptococcus (10-12), antibodies to the Type III-specific capsular polysaccharide of pneumococcus (13,14), rabbit antihapten (15), and specimens of antibodies and of Fab' fragments which crystallized (Nisonoff et al., in references 16,17), but sequence data on these are not yet available.The large body of sequence data related to immunoglobulin structure comes from the analysis of urinary Bence Jones proteins and from the monoclonal immunoglobulins found in large amounts in the sera of patients with multiple myeloma and Waldenstrtim macroglobuUnemia (16,18). While a substantial body of evidence was available relating these proteins to immunoglobulins, the recent demonstration that many myeloma globulins have specific ligand-binding properties like those of many antibodies provides increasing confidence that myeloma globulins represent homogeneous populations of antibody molecules (16,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27).

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“…(28)(29)(30)(31)(32)(33)(34). A similar situation probably exists for X1 and X2, because the amino acid sequence in the V segment of L3I5 resembles so closely that of L"04 and other A chains (12,23); thus, VA can be associated with Cx1 or CX2.…”

Section: Asx Glx Gly His Thr ---------Val Glx Lys Ser Leu Ser Pro Alamentioning

confidence: 89%

Amino Acid Sequence of the Light Chain from a Mouse Myeloma Protein with Anti-Hapten Activity: Evidence for a Third Type of Light Chain

Schulenburg¹,

Simms²,

Lynch³

et al. 1971

Proc. Natl. Acad. Sci. U.S.A.

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A tentative amino acid sequence has been determined for the light chain of a mouse A-myeloma (MOPC-315) protein with anti-2,4-dinitrophenyl activity. An unusual amino acid sequence in the carboxyl-terminal 104 residues suggests that the chain represents a new class of immunoglobulin light chain. The "variable" segment of this chain (amino-terminal 110 residues) differs at only eight positions from the corresponding segment of the lambda chain of a mouse M-myeloma (MOPC-104) protein with anti-dextran activity.The recent finding of myeloma proteins with antibody activity (e.g., 1-3) and the development of procedures for the preparation of conventional antibodies of remarkably restricted heterogeneity (4, 5) provide opportunities to correlate the primary structure of immunoglobulins and their specific reactivities with particular haptens and antigens. Accordingly, we are studying the structure of protein 315, an A-myeloma protein that binds 2,4-dinitrophenyl (Dnp) ligands with high specificity (6). In this paper, we present a tentative amino acid sequence for the light chain (LI5) of this protein. An unusual sequence suggests that this chain represents a new type, resembling immunoglobulin light chains of the X type more than those of the K type.Protein 315 was isolated from sera of mice bearing tranisplants of MOPC-315, a plasma cell tumor*, whose origin is described below. Fully reduced carboxymethylated or aminoethylated light chains were prepared as described (40), and digested with trypsin, thermolysin, or pepsin. The peptides were purified by ion-exchange chromatography on Dowex resins (7) or SE-Sephadex (8), and their amino acid sequences were determined by Edman degradation (9). The successively removed amino-terminal residues were identified by: subtractive analysis, gas-liquid chromatography of CH3CNS amino acids (9), the dansyl procedure (10) G-100 in 5 M guanidine -HCl, followed by chromatography on CM-cellulose in 8 M urea (11). Antisera to LI'' were prepared by immunizing rabbits with the Fab fragment of protein 315 in complete Freund's adjuvant, and absorbing the sera with K-and X-containing A-myeloma proteins that were produced by plasma cell tumors MOPC-460 and S-176*.A complete set of peptides was not isolated from any one enzymatic digest, but a combination of peptides from trypsin and thermolysin digests accounted for the amino acid composition of the chain (Table 1), and provided the basis for the provisional sequence shown in Fig. 1. As few overlaps have been established thus far, the alignment of peptides was based largely on homology with the complete amino acid sequence of the mouse X light chain that is produced by plasma cell tumor MOPC-104 (12); this light chain is hereafter referred to as L104. There are two methionine residues in L315, and the three purified cyanogen bromide fragments obtained from this chain (corresponding to the N-terminal 87 residues, the central 88 residues, and the C-terminal 39

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Subgroups of Amino Acid Sequences in the Variable Regions of Immunoglobulin Heavy Chains

Abstract: Abstract.-The amino acid sequence of the first 133 residues of the heavy (y) chain from a human yG immunoglobulin (He)

Cited by 73 publications

References 19 publications

Macroglobulin Structure: Variable Sequence of Light and Heavy Chains

Macroglobulin Structure: Variable Sequence of Light and Heavy Chains

An Analysis of the Sequences of the Variable Regions of Bence Jones Proteins and Myeloma Light Chains and Their Implications for Antibody Complementarity

Amino Acid Sequence of the Light Chain from a Mouse Myeloma Protein with Anti-Hapten Activity: Evidence for a Third Type of Light Chain

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