Journal
JOURNAL OF NEUROIMMUNOLOGY
Volume 205, Issue 1-2, Pages 94-100Publisher
ELSEVIER
DOI: 10.1016/j.jneuroim.2008.09.013
Keywords
Prion protein; Monoclonal antibodies; Epitope recognition; Immunocooperativity
Categories
Funding
- National Heart, Lung and Blood Institute [1RO1 HL63837]
- Health Science Center Research Initiative
- US Army Medical Research and Materiel Command [DAMD17-03-1-0368]
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We have characterized the antibody-antigen binding events of the prion protein (PrP) utilizing three new PrP-specific monoclonal antibodies (Mabs). The degree of immunoreactivity was dependent on the denaturation treatment with the combination of heat and SDS resulting in the highest levels of epitope accessibility and antibody binding. Interestingly however. this harsh denaturation treatment was not sufficient to completely and irreversibly abolish protein conformation. The Mabs differed in their PrP epitopes with Mab 08-1/11F12 binding in the region of PrP93-122, Mab 08-1/8E9 reacting to PrP155-200 and Mab 08-1/5D6 directed to an undefined conformational epitope. Using normal and infected brains from hamsters, sheep and deer, we demonstrate that the binding of PrP to one Mab triggers PrP epitope unmasking, which enhances the binding of a second Mab. This phenomenon, termed positive immunocooperativity, is specific regarding epitope and the sequence of binding events. Positive immunocooperativity will likely increase immunoassay sensitivity since assay conditions for PrPsc detection does not require protease digestion. (C) 2008 Elsevier B.V. All rights reserved.
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