The Use of Hybridomas to Localize Mouse Immunoglobulin Genes

Hengartner, Hans; T, Meo; Müller, Edith

doi:10.1007/978-1-4615-7505-4_5

Cited by 2 publications

(2 citation statements)

References 21 publications

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“…When X-44 is compared to T-601 it can be seen that the Trp-Ile interchange at 96 L results in the replacement of a nonpolar side chain by a large, polar, ring-structured side chain. The similarity in KaS of these two proteins suggests that the Trp-Ile interchange is accomodated without significantly altering affinity for 13 (1,6)galactan haptens. This observation, in conjunction with the large number of complementarity-determining region differences which appear not to change affinity or specificity, suggests that, in this system, alternative amino acids introduced at 96 L by the J segment do not generate functional binding site diversity.…”

Section: Discussionmentioning

confidence: 99%

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kappa Chain joining segments and structural diversity of antibody combining sites.

Rudikoff¹,

Rao²,

Glaudemans³

et al. 1980

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

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Immunoglobulin K light chains are coded for by at least three distinct gene segments designated variable, joining, and constant. The joining gene codes for the 13 amino acid segment linking the variable and constant regions. This peptide includes the last amino acid (96) in the third complementarity-determining region and thus could introduce structural diversity. We have determined the light chain variable region sequences from three myeloma proteins with P(1,6)galactan-binding specificity, bringing to six the number of light chains sequenced from proteins demonstrating this specificity. Five of these have isoleucine at position 96 and the sixth tryptophan. This substitution appears to be accommodated with no significant change in association constant for a 19(1,6)galactan hapten. Additionally, as many as nine substitutions are found in both light and heavy chain complementarity-determining regions between members of this group-although only minimal variations in hapten binding affinity are observed. The isoleucine found at position 96 in five of the X chains could not be coded for by any of the joining gene nucleotide. sequences previously observed and would require a novel nucleotide sequence at the recombination site between variable and joining genes to produce the observed protein structure. Alternatively, there may exist joining gene segments not yet detected. The study of antibody structure and diversity has long been of great interest in the field of immunology. The immunoglobulin molecule is composed of two polypeptide chains designated light (L) and heavy (H), each of which is encoded on a separate chromosome (1). Each of these two chains in turn is coded for by at least three distinct genetic regions termed variable (V), constant (C), and joining (J). The V regions of both H and L chains exhibit primary amino acid sequence differences that are responsible for the great variety of antigen binding specificities exhibited by vertebrate organisms. All L chain C regions may be divided into two classes, K and X; the corresponding region in heavy chains may represent several classes-i.e., jA y, a, 6, and e.Recent studies at both the protein (2-4) and nucleic acid levels (5, 6) have identified a third segment of the immunoglobulin chain, the J segment which bridges the V and C regions. The size and boundaries of this segment have been defined for mouse K chains and include the last residue in the third complementarity-determining region. A corresponding J segment has been identified in H chains by protein sequence determination (4, 7) and by nucleic acid analysis (8).For a number of years this laboratory has attempted to explore various aspects of antibody structure and diversity by analyzing groups of antigen-binding myeloma proteins. One such group is composed of proteins with binding specificity for 3(1,6)-linked galactan moieties. Six of these proteins have been studied in terms of specificity (9, 10), structure (3, 4, 11), and idiotypy (12). We have reported the L chain V region sequences from ...

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Section: Discussionmentioning

confidence: 99%

“…One such group is composed of proteins with binding specificity for 3 (1,6)-linked galactan moieties. Six of these proteins have been studied in terms of specificity (9,10), structure (3,4,11), and idiotypy (12).…”

mentioning

confidence: 99%

kappa Chain joining segments and structural diversity of antibody combining sites.

Rudikoff¹,

Rao²,

Glaudemans³

et al. 1980

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

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Multiple organ-reactive monoclonal autoantibodies

Haspel

Onodera

Prabhakar

et al. 1983

Nature

142

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Autoantibodies directed against a wide range of normal tissue antigens have been found in the sera of patients with autoimmune diseases. It is generally thought that different and specific autoantibodies react with different tissues but the possibility exists that some autoantibodies may react with common antigens found in different tissues and organs. Recently, we showed that mice infected with reovirus developed a polyendocrine disease with autoantibodies to the pancreas, anterior pituitary, thymus and gastric mucosa. Using hybridoma technology, we obtained a number of monoclonal autoantibodies which reacted with antigens in single organs. We now report the production and pattern of reactivity of seven multiple organ-reactive monoclonal autoantibodies. By using antibody-affinity columns, autoantigens also have been isolated and their molecular weights determined. The results suggest that monoclonal multiple organ-reactive autoantibodies react either with the same molecule present in several organs or with common antigenic determinants on different molecules in multiple organs. In either case, the existence of multiple organ-reactive antibodies may be a partial explanation for multiple organ autoimmunity.

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The Use of Hybridomas to Localize Mouse Immunoglobulin Genes

Cited by 2 publications

References 21 publications

kappa Chain joining segments and structural diversity of antibody combining sites.

kappa Chain joining segments and structural diversity of antibody combining sites.

Multiple organ-reactive monoclonal autoantibodies

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