EFFECTS OF SECONDARY FORCES ON A HIGH-AFFINITY MONOCLONAL IGM ANTIFLUORESCEIN ANTIBODY POSSESSING CRYOGLOBULIN AND OTHER CROSS-REACTIVE PROPERTIES

The effects of secondary forces on monoclonal IgM anti-fluorescein ant ibody 18-2-3 reactivity were investigated and the results correlated w ith similar studies characterizing anti-fluorescein mAbs 4-4-20 and 9- 40. mAb 18-2-3 was considered an important model for further elucidati on of secondary forces since it possessed ligand binding properties si milar to mAb 4-4-20, such as a similar affinity, but due to a very dif ferent primary structure it was idiotypically and metatypically distin ct. mAb 18-2-3 also possessed cryoglobulin (anti-Ig) and extensive cro ss-reactive properties (e.g. anti-phenyloxazolone) suggestive of an at ypical anti-fluorescein active site. The reactivity of mAb 18-2-3 with model fluorescein-peptides was modulated by secondary forces in a man ner that differed from both mAbs 4-4-20 and 9-40. Thus, the effects of secondary forces seemed to vary with each monoclonal antibody even th ough each of the immunoglobulins studied were specific for the same ho mologous ligand. Results indicated that secondary forces impacted immu ne complex stability, variable domain conformation and protein dynamic s. Models were postulated to account for secondary effects on the mAb 18-2-3 active site relative to mAbs 4-4-20 and 9-40. Levels of hydrati on, active site architecture and local amino acid dynamics were among the models cited. (C) 1998 Elsevier Science Ltd. All rights reserved.