Linked Life Data

7688391

Source:http://linkedlifedata.com/resource/pubmed/id/7688391

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1993-9-8
pubmed:abstractText
The framework regions of antibodies fold into a conserved beta-sheet structure that acts as scaffolding for the antigen-contacting complementarity-determining regions (CDR). To test the structural equivalence of the frameworks between two antibodies with widely different combining sites, we created chimeric H and L chains by grafting the CDR of an alpha(1-->6)dextran specific antibody onto the framework of a p-azophenylarsonate (Ars) specific antibody through oligonucleotide-directed mutagenesis of the anti-Ars variable region genes. Antibodies consisting of various chain combinations of the chimeric, anti-dextran, and anti-Ars derived H and L chains were generated in transfectomas and tested for binding to dextran and Ars. Of the newly created chimeric and/or hybrid antibodies, an antibody with the chimeric H chain and the anti-dextran L chain bound to dextran with the same association constant as the parental anti-dextran antibody, and like the anti-dextran antibody was shown by immunochemical mapping to have a site complementary to six glucose residues. None of the other new variable region combinations, including the all-chimeric combination, showed binding to either dextran or Ars. These results indicate that the H chain but not the L chain anti-dextran and anti-Ars frameworks are functionally equivalent. Attempts to confer dextran binding on the H and L chain chimeric antibody, by mutagenizing selected framework residues, were unsuccessful. This study demonstrates the important role of the frameworks in the precise alignment of the CDR for Ag binding.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
151
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1968-78
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Chimeric antibodies with anti-dextran-derived complementarity-determining regions and anti-p-azophenylarsonate-derived framework regions.
pubmed:affiliation
Department of Biochemistry, Boston University School of Medicine, MA 02118.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.