title: Alteration of apparent specificity of monoclonal (hybridoma) antibodies recognizing polymorphic histocompatibility and blood group determinants.
abstract: The fine specificity of five mouse anti-chicken monoclonal antibodies was altered by changes in pH or temperature. Four of these antibodies recognized determinants of the MHC, and the fifth recognized another polymorphic erythrocyte antigen. The pH changes could alter a monoclonal antibody specificity from an apparently private determinant to an apparently public determinant. These alterations have been interpreted on the basis of the pH effect on binding affinity, relative to the threshold of the assay used. Consistent with this interpretation was the observation that bound antibodies were eluted most rapidly from a "cross-reacting" antigen, even at a pH where cross-reactions were strongest. Also, an increase in the valency of the monoclonal antibody resulted in an increase in the observed degree of cross-reaction. This was demonstrated in a highly multivalent antibody-directed rosette assay (ADRA), where the cross-reactions occurred over a wider pH range. These results have considerable importance for the use of monoclonal antibodies as monospecific reagents, especially in highly polymorphic systems such as the MHC. Also, these results suggest ways to improve the apparent specificity of particular monoclonal antibodies, e.g., by removing undesirable cross-reactions.
mesh_terms: D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D001666:Binding Sites, Antibody; D002645:Chickens; D002999:Clone Cells / Q000276:immunology; D003429:Cross Reactions; D000939:Epitopes; D006384:Hemagglutination; D006649:Histocompatibility Antigens; D006822:Hybrid Cells / Q000276:immunology; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008808:Mice, Inbred CBA; D012397:Rosette Formation
chemical_list: D000939:Epitopes; D006649:Histocompatibility Antigens