Three Variable-Gene Pools common to IgM, IgG and IgA Immunoglobulins

Köhler, Heinz; Shimizu, Akira; Paul, C.; Moore, Virginia; Putnam, Frank W.

doi:10.1038/2271318a0

Cited by 110 publications

(32 citation statements)

References 22 publications

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“…Similarly, structural studies on antibodies to p-azophenylarsonate induced in mice (35) (14); identical NH2-terminal light chain sequences through the first hypervariable region have also been found in two human IgG anti-y-globulins (17) and in rabbit antibodies against streptococcal polysaccharides (18). There analysis (38,39) and on idiotype studies (40) and is consistent with the accepted view that at least two genes are coding for one polypeptide chain (41). The NH2-terminal 36 residues of the human ,u chain FR document the extraordinary fact that within an evolutionary span of about 75 million years (42) a sequence was preserved that differs from the mouse heavy chain sequences by only four amino acid substitutions.…”

Section: Resultssupporting

confidence: 63%

Human and murine phosphorycholine-binding immunoglobulins: conserved subgroup and first hypervariable region of heavy chains.

Riesen¹,

Braun²,

Jaton³

1976

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

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The NH2-terminal 36 residues of the heavy chain and the NH-terminal 40 residues of the light chain from a human Waldenstr6m's IgM with binding activity for phosphorylcholine (phosphocholine) are compared with the published sequences of five mouse IgA myeloma proteins with the same activity. An extensive structural similarity, i.e., 3 amino acid interchanges within framework residues, and one in the hypervariable region, is noted between the heavy chains of both species. The light chains, however, show a considerable diversity and, in contrast to the heavy chain, no correlation between the primary structure of the first hypervariable region and the binding specificity is apparent.

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Section: Resultssupporting

confidence: 63%

Human and murine phosphorycholine-binding immunoglobulins: conserved subgroup and first hypervariable region of heavy chains.

Riesen¹,

Braun²,

Jaton³

1976

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

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“…The subclass Theria contains two infraclasses, Metatheria (pouched mammals) and Eutheria (placental mammals). The heavy chain result in the opossum (a pouched mammal) assumed particular interest because, although the sequence of the first 11 residues of the pool showed unequivocally that this preparation was assignable to the Vmii subgroup, the residue at position 2 was an isoleucine rather than the valine that is characteristic of VlcIIII proteins (30,13). This undoubtedly represents a "phylogenetically associated" residue (10) and merits further analysis in other members of the Metatheria.…”

Section: Discussionmentioning

confidence: 99%

Phylogenetically Associated Residues Within the Vhiii Subgroup of Several Mammalian Species

Capra

Wasserman

Kehoe

1973

The Journal of Experimental Medicine

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The origin of the amino acid sequence diversity characteristic of the variable (V) regions of immunoglobulins has been the subject of considerable controversy for several years. Two types of theories have been proposed to account for this diversity, primarily on the basis of sequence data derived from light chains. "Pauci-gene" theories assume that there are relatively few variable region genes in the germ llne and that the many different variable region sequences required for the humoral antibody response are generated by some somatic process (1-4). Multi-gene, or germ line, theories assume, alternatively, that a full complement of variable region genes exists preformed in the germ line (5, 6). A clear choice between a pauci-or multi-gene theory will probably have to await direct analyses of lymphoid cell DNA. However, RNA hybridization studies that have been carried out to date (7, 8) have not settled the question unambiguously.Major challenges to the validity of multi-gene theories are their difficulty in explaining the origin and stability of the allotypic markers present in the variable regions of rabbit heavy chains and the finding of "species-specific residues" in immunoglobulin light chains (9). Completely satisfactory explanations of these features of ilnmunoglobulin structure have not yet been provided under multi-gene assumptions.The exact identity and distribution of the species-specific (or phylogenetically associated, ref. 10) residues have not been easy to determine because of the several variable region subgroups that are characteristic of the light chains of most species. The presence of the subgroups makes difficult the identification of such residues in pooled light chains from a single species, an approach that would be of enormous value in establishing their true significance.Previous studies of heavy chains prepared from myeloma proteins have shown that the primary structure of the variable region of proteins in the V n m subgroup is extremely conserved in at ]east four species, and that phylogenetically

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“…These ensembles of related sequences, first noted for light chains (6)(7)(8), are referred to as variable region subgroups and are found in both kappa and lambda light chains. More recently, four subgroups have been identified in heavy chains (9)(10)(11)(12). Of the four, only the VHIII subgroup has an unblocked (i.e., not pyrollidone carboxylic acid) aminoterminal residue.…”

mentioning

confidence: 99%

Sequence Relationships among the Variable Regions of Immunoglobulin Heavy Chains from Various Mammalian Species

Kehoe

Capra

1972

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

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Immunoglobulin heavy chains of myeloma proteins from dogs and cats have been subjected to automated sequence analysis. When the results were compared with human heavy-chain sequences, all the dog and cat proteins could be unequivocally assigned to the VHIII subgroup. This pattern contrasts with that in human proteins in which only 25% of all heavy chains sequenced belong to this subgroup. The 30 residues at the NH2 termini of dog, cat, and human heavy chains had sequence identities near or exceeding 90%, in contrast to established interspecies sequence homologies of constant regions of about 60%. Some genes of the immunoglobulin heavy-chain variable region thus appear to have been conserved through a considerable period of evolutionary time.The analyses also showed that the presence of certain amino acids at certain positions in these heavy chains could be correlated with the species of origin. The occurrence of such "phylogenetically associated" residues is most consistent with the presence of a restricted number of genes in the heavy-chain variable region pool.Both heavy (H) and light (L) polypeptide chains of immunoglobulins contain two distinct regions from the standpoint of variability of amino-acid sequence (1, 2). The variable (V) region is found in the amino-terminal portion of each chain and is believed to participate in the antigen-binding function of these molecules. The constant (C) region comprises the balance of each chain and, in the heavy chain, mediates the biological, or effector, properties characteristic of many immunoglobulins (3). Several lines of evidence suggest that the variable and constant regions of a given H or L chain are encoded by separate genes (4, 5).The pattern of sequence variability among variable regions is such that certain collections of individual sequences are much more closely related to each other than to other variable region sequences. These ensembles of related sequences, first noted for light chains (6-8), are referred to as variable region subgroups and are found in both kappa and lambda light chains. More recently, four subgroups have been identified in heavy chains (9)(10)(11)(12). Of the four, only the VHIII subgroup has an unblocked (i.e., not pyrollidone carboxylic acid) aminoterminal residue.Sequence analyses of heavy-chain variable regions of an unselected series of homogeneous myeloma proteins isolated from dogs and cats are reported here. A comparison of these sequences with certain human proteins suggests an unanticipated degree of evolutionary stability for certain genes of the immunoglobulin variable region. MATERIALS AND METHODSThe source and methods of preparation of the various myeloma proteins have been reported elsewhere (13,14). IgG fractions were prepared from pooled sera by DEAESephadex ion-exchange chromotography. Purified heavy chains were subjected to direct sequence analysis on a Beckman model 890A automated sequencer (15). RESULTS AND DISCUSSIONThe relevant variable region sequences are shown in Fig. 1. The canine and feline heavy ...

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Three Variable-Gene Pools common to IgM, IgG and IgA Immunoglobulins

Cited by 110 publications

References 22 publications

Human and murine phosphorycholine-binding immunoglobulins: conserved subgroup and first hypervariable region of heavy chains.

Human and murine phosphorycholine-binding immunoglobulins: conserved subgroup and first hypervariable region of heavy chains.

Phylogenetically Associated Residues Within the Vhiii Subgroup of Several Mammalian Species

Sequence Relationships among the Variable Regions of Immunoglobulin Heavy Chains from Various Mammalian Species

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