Comparison of monoclonal antibodies to the deeper core region of gram-negative lipopolysaccharide by means of polymyxin B inhibition studies.
Previously we have described a panel of 12 monoclonal antibodies (Mabs) directed to lipopolysaccharide (LPS) of the Salmonella minnesota Re mutant R595. Six of them had been found to decrease mortality of LPS for actinomycin D-sensitized mice. The other six clones were not effective. It is known and we have confirmed that polymyxin B (PMB) also neutralizes LPS endotoxicity. We now tested the hypothesis that protective clones bound near or at the PMB binding site, by an in vitro assay where PMB and Mab competed for binding to R595 LPS. Our results show that this hypothesis must be rejected and that the LPS epitopes recognized by protective clones are interspersed by those recognized by non-protective ones. We could, however, demonstrate that this sort of inhibition assays are of value in estimating the localization on the core of the binding sites of various Mabs.
Appelmelk
B J
BJ
Department of Medical Microbiology, Vrije Universiteit, School of Medicine, Amsterdam, The Netherlands.
Verweij-van Vught
A M
AM
Maaskant
J J
JJ
Schouten
W F
WF
Thijs
L G
LG
MacLaren
D M
DM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000936:Antigen-Antibody Complex; D004797:Enzyme-Linked Immunosorbent Assay; D006090:Gram-Negative Bacteria / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D011112:Polymyxin B; D011113:Polymyxins; D012475:Salmonella / Q000276:immunology*; D014115:Toxemia / Q000276:immunology / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D008070:Lipopolysaccharides; D011113:Polymyxins; D011112:Polymyxin B