Role of immunogen design in induction of soman-specific monoclonal antibodies.
The study of monoclonal antibodies raised against defined hapten epitopes has been a useful approach to understanding antibody repertoire. The situation in which antibodies are raised against different epitopes of the same hapten but have some common recognition or binding features has been less frequently examined. To explore the latter situation, we have characterized three monoclonal antibodies previously raised against two structurally different epitopes of the same organophosphorus nerve agent hapten, pinacolymethyl phosphonofluoridate (soman). Two antibodies, BE2-IA10 (BE2) and CC1-IIA4 (CC1), raised against the hydrophobic pinacolyl motif of soman, bind exclusively to soman and not to any other organophosphorus nerve agents. We determined that these antibodies have the same heavy chain sequence, which they share with the unrelated antibodies MOPC 21 and H17-L19. While all these antibodies share the same heavy chain sequence, they each possess different light chain sequences. Binding studies revealed that each of these antibodies has a unique reactivity with a panel of structurally related ligands, suggesting that the light chains are critically important in determining specificity in these antibodies. The third antibody, #2.ID8.2, raised against the methyl phosphoryl portion of soman, has unique heavy and light chain sequences. This antibody binds to all the currently identified chemical warfare agents. Given that the presenting epitope used to induce #2.ID8.2 is common to sarin, soman, tabun and VX, the ability of this antibody to recognize each of these haptens versus the inability of BE2 or CC1 to do so demonstrates the important role that immunogen design can play in the specificity of an antibody response.
Johnson
Jennifer K
JK
Department of OCBS, University of Maryland, 666 West Baltimore Street, Baltimore, MD 21201, USA.
Cerasoli
Douglas M
DM
Lenz
David E
DE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D001666:Binding Sites, Antibody; D006825:Hybridomas; D007124:Immunoenzyme Techniques; D051379:Mice; D012999:Soman / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D014614:Vaccines, Synthetic; D012999:Soman