Monoclonal Anti-Lipid A IgM Antibodies HA-1A and E-5 Recognize Distinct Epitopes on Lipopolysaccharide and Lipid A

Abstract
Specific binding of two monoclonal IgM antibodies previously investigated as therapeutic agents for treating gram-negativeseptic shock,HA-1A and E5, wasassessedwith respect to lipid A and lipopolysaccharide(LPS). Both antibodies bound to lipid A; however, binding ofHA-lA wassignificantlygreater than that of E5 to LPS derivedfrom rough strains of bacteria. Reciprocal competitive inhibition experiments supported the concept that HA-IA and E5 bind to distinct epitopes on lipid A. Further, competitiveinhibition studies usinga monoclonalantiidiotype antibody with specificity for the variableregion ofHA-1A suggestedthat HA-1A and E5 do not share a common idiotype. Finally, studies using double-strandedDNA as antigen indicated that E5 but not HA-1A will bind to DNA. Collectively, these data indicate that HA-1A and E5 are different lipid A-specific antibodies that bind to distinct epitopes on lipid A.

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