Binding properties of immunoglobulin combining sites specific for terminal or nonterminal antigenic determinants in dextran.

Abstract

Binding constants of the dextran-reactive BALB/c mouse IgA myeloma proteins W3129 and QUPC 52 have been determined for each member of the isomaltose series of oligosaccharides and for methyl alphaDglucoside. Protein W3129 has maximum complementarity for isomaltopentaose (IM5) deltaf degrees = 7,180 cal/mol) with 55-60% of the total binding energy directed against methylalphaDglucoside. Protein QUPC 52 gives maximum binding with isomaltohexaose (IM6) (deltaF degrees = -5,340 cal/mol) and has about 70% of its total binding energy for isomaltotriose (IM3), but at most only 5% for isomaltose (IM2) or methyl alphaDglucoside. Protein W3129 precipitates with branched dextrans high in alpha (1 yields 6) linkages and reacts with but does not precipitate a synthetic alpha (1 yields 6)-linked linear dextran. Protein QUPC 52 precipitates both branched and linear dextrans. Thus, the immunodominant group for protein W3129 is mimicked by methyl alphaDglucoside and this protein reacts exclusively at the terminal nonreducing ends of alpha (1 yields 6)-linked dextran chains. Protein QUPC 52 has an immunodominant group which is expressed by IM3 but not smaller oligosaccharides and this protein can react at nonterminal locations along alpha (1 yields 6)- linked dextran chains.Precipitation of linear dextran seems to be a valid although not quantitative assay for antidextrans with nonterminal specificity. Quantitative precipitin reactions with branched and linear dextrans suggest that alpha (1 yields 6)-specific human antidextrans are mixtures of molecules having terminal and nonterminal specificities and that the fraction of each type can vary among individuals. Rabbit antisera against IM3 or IM6 coupled to bovine serum albumin also appear to contain antibodies with nonterminal specificity for dextran chains although a large fraction has terminal specificity. Low molecular weight clinical dextran N-150N (congruent to 60,000) reacted more like linear dextran than like its parent native-branched dextran B512. This is thought to result from an abundance of nonterminal determinants in clinical dextran N-150N but a very small number of functional terminal determinants per molecule. An appreciation of terminal and nonterminal specificities and of the different immunodominant structures in isomaltosyl chains has proven to be of a great value in understanding the immunochemical reactions of dextrans. Moreover, certain previous findings with fructosan-reactive mouse myeloma proteins and human antilevans (55, 84) also suggest terminal and nonterminal specificities for levan chains.

A polysaccharide from Streptococcus sanguis 34 that inhibits coaggregation of S. sanguis 34 with Actinomyces viscosus T14V

“…Whereas these findings suggest that the OL-4 structure makes a major contribution to antigenicity, the location of the respective determinant within the polysaccharide is not known. Since the CIP is linear, antibodies that are inhibited by OL-4 may react with repeating nonterminal antigenic determinants, as has been found with antibodies that precipitate linear chains of al-6-linked dextran (11). However, CIP molecules with multiple nonreducing ends would occur if branching were present or if linear chains were cross-linked by cell wall peptidoglycan.…”

Structures of synthetic O-antigen fragments from serotype 2aShigella flexneriin complex with a protective monoclonal antibody

“…Early work on anti-polysaccharide antibodies suggested that carbohydrate epitopes could vary from one to approximately seven residues, the upper limit being determined by the surface available at the antigen-binding site (16). It was concluded that small epitopes generally include the nonreducing terminal residue, whereas larger epitopes are located along the length of the polysaccharide chain (17). It was further suggested that small epitopes bind to cavity-type antigen-binding-site topologies, whereas larger internal epitopes are recognized by groove-type topologies (18).…”

Capsular polysaccharide vaccine for Group BNeisseria meningitidis,Escherichia coliK1, andPasteurella haemolyticaA2

“…This cross-reactivity between GBM and GCM is not an unexpected effect, because several references describe the superior immunogenicity of the terminal nonreducing end of polysaccharides and the similar region of polypeptides (51)(52)(53)(54).…”