Biomaterial Database

Complete variable region sequences of five homologous high affinity anti-digoxin antibodies. 1987

D J Panka, and M N Margolies

Department of Medicine, Massachusetts General Hospital, Boston.

High affinity murine A/J anti-digoxin monoclonal antibodies exhibit diversity in binding specificity for structurally related cardiac glycosides. They utilize several VH and VL genes. Among this diverse set, however, five antibodies share V region amino-terminal sequences that are remarkably homologous. The five antibodies were divided into three subsets based on different fine specificity-binding patterns. Therefore, complete V region sequences were determined by Edman degradation and by nucleotide sequence analysis. The VH region homology among the five antibodies was 84 to 100% and the VL region homology was 89 to 99%. The sequence data are consistent with the use of single (or closely related) VH and VL genes encoding the five antibodies. Four antibodies, derived from the same fusion (40-40, 40-120, 40-140, and 40-160), use identical D, JH2, and JK5 gene segments and identical junctions suggesting that they are clonally related. The fifth antibody (35-20) uses different D and JH1 gene segments but the same JK5 gene segment. All five antibodies share a cross-reactive idiotype. The three antibodies that exhibit the greatest degree of homology (40-40, 40-120, and 40-140) also share indistinguishable antigen-binding patterns as well as private idiotopes not present on the other two antibodies. Antibody 40-160, which has the next most homologous sequence, shares idiotopes with the first set but binds preferentially to different sites on the hapten, whereas antibody 35-20 has the most divergent sequence. In general, the degree of sequence homology among the five antibodies correlates with their hierarchical order based on hapten and idiotype fine specificity patterns.

UI	MeSH Term	Description	Entries
D007130	Immunoglobulin Idiotypes	Unique genetically-controlled determinants present on ANTIBODIES whose specificity is limited to a single group of proteins (e.g., another antibody molecule or an individual myeloma protein). The idiotype appears to represent the antigenicity of the antigen-binding site of the antibody and to be genetically codetermined with it. The idiotypic determinants have been precisely located to the IMMUNOGLOBULIN VARIABLE REGION of both immunoglobin polypeptide chains.	Idiotypes, Immunoglobulin,Ig Idiotypes,Idiotype, Ig,Idiotype, Immunoglobulin,Idiotypes, Ig,Ig Idiotype,Immunoglobulin Idiotype
D007135	Immunoglobulin Variable Region	That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.	Variable Region, Ig,Variable Region, Immunoglobulin,Framework Region, Immunoglobulin,Fv Antibody Fragments,Fv Fragments,Ig Framework Region,Ig Variable Region,Immunoglobulin Framework Region,Immunoglobulin Fv Fragments,Immunoglobulin V,Antibody Fragment, Fv,Antibody Fragments, Fv,Fragment, Fv,Fragment, Fv Antibody,Fragment, Immunoglobulin Fv,Fragments, Fv,Fragments, Fv Antibody,Fragments, Immunoglobulin Fv,Framework Region, Ig,Framework Regions, Ig,Framework Regions, Immunoglobulin,Fv Antibody Fragment,Fv Fragment,Fv Fragment, Immunoglobulin,Fv Fragments, Immunoglobulin,Ig Framework Regions,Ig Variable Regions,Immunoglobulin Framework Regions,Immunoglobulin Fv Fragment,Immunoglobulin Variable Regions,Regions, Immunoglobulin Variable,Variable Regions, Ig,Variable Regions, Immunoglobulin
D008805	Mice, Inbred A	An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research.	Mouse, Inbred A,Inbred A Mice,Inbred A Mouse
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D002301	Cardiac Glycosides	Cyclopentanophenanthrenes with a 5- or 6-membered lactone ring attached at the 17-position and SUGARS attached at the 3-position. Plants they come from have long been used in congestive heart failure. They increase the force of cardiac contraction without significantly affecting other parameters, but are very toxic at larger doses. Their mechanism of action usually involves inhibition of the NA(+)-K(+)-EXCHANGING ATPASE and they are often used in cell biological studies for that purpose.	Cardiac Glycoside,Cardiotonic Steroid,Cardiotonic Steroids,Glycoside, Cardiac,Glycosides, Cardiac,Steroid, Cardiotonic,Steroids, Cardiotonic
D003429	Cross Reactions	Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.	Cross Reaction,Reaction, Cross,Reactions, Cross
D004077	Digoxin	A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone DIGOXIGENIN. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in ATRIAL FIBRILLATION and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666)	Digacin,Digitek,Digoregen,Digoxina Boehringer,Digoxine Nativelle,Dilanacin,Hemigoxine Nativelle,Lanacordin,Lanicor,Lanoxicaps,Lanoxin,Lanoxin-PG,Lenoxin,Mapluxin,Boehringer, Digoxina,Lanoxin PG,Nativelle, Digoxine,Nativelle, Hemigoxine
D005803	Genes, Immunoglobulin	Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity).	Genes, Ig,Immunoglobulin Genes,Gene, Ig,Gene, Immunoglobulin,Ig Gene,Ig Genes,Immunoglobulin Gene
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia