Immunology of chondroitin/dermatan sulfate.
Variable substitutions and locations of the sulfate esters along the backbone of chondroitin/dermatan sulfate chains, combined with their carbohydrate structures, present topographies to immune systems which can be recognized as antigenic. This has led to the development of a number of monoclonal antibodies which recognize distinct epitopes in the native structures of these glycosaminoglycan chains. In some studies, the original chondroitin/dermatan sulfate proteoglycan was digested with chondroitinase enzymes before being used as an immunogen. in this case, the linkage oligosaccharides remaining bound to the core protein contain a modified (4,5-unsaturated) hexuronic acid derivative at their non-reducing ends as a result of the eliminase mechanism of the enzyme. This 'haptenic' structure is highly antigenic and has led to the development of a number of monoclonal antibodies which recognize this structure as part of their epitopes. Examples of the use of some of these monoclonal antibodies for localization of proteoglycan structures in tissue sections and on transblots are described. The precise structures are known for only a few of the native epitopes recognized by these monoclonal antibodies. Recent analytical methods have been developed for determining structures of chondroitin sulfate oligosaccharides. An example of the use of these methods to analyze the structures of the non-reducing termini of chondroitin/dermatan sulfate chains is discussed. The results show their potential value for quantifying the native epitope recognized by a monoclonal antibody, designated 3B3, which recognizes chains terminated by glucuronic acid-N-acetylgalactosamine-6-sulfate. Such methods should be useful for determining the epitope structures for other monoclonal antibodies in this class.
Hascall
V C
VC
Department of Biomedical Engineering, Cleveland Clinic Foundation, Ohio, USA.
Midura
R J
RJ
Sorrell
J M
JM
Plaas
A H
AH
D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D000941:Antigens / Q000276:immunology*; D002240:Carbohydrate Sequence; D002809:Chondroitin Sulfates / Q000737:chemistry / Q000276:immunology*; D003871:Dermatan Sulfate / Q000737:chemistry / Q000276:immunology*; D000939:Epitopes / Q000032:analysis; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure
D000911:Antibodies, Monoclonal; D000941:Antigens; D000939:Epitopes; D003871:Dermatan Sulfate; D002809:Chondroitin Sulfates