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On the roles of polyvalent binding in immune recognition: Perspectives in the nanoscience of immunology and the immune response to nanomedicines

Journal

ADVANCED DRUG DELIVERY REVIEWS
Volume 64, Issue 15, Pages 1759-1781

Publisher

ELSEVIER
DOI: 10.1016/j.addr.2012.06.003

Keywords

Polyvalent binding; Avidity; Adhesion molecules; Integrins; Immunoglobulins; Mannan-binding lectin; Nanotoxicology

Funding

  1. Danish Multiple Sclerosis Association
  2. Danish Rheumatism Association
  3. Carlsberg Foundation
  4. Novo Nordisk Foundation
  5. Lundbeck Foundation
  6. LEO Pharma Research Foundation
  7. Danish Council for Independent Research\Medical Sciences
  8. Danish Council for Independent Research\ Natural Sciences

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Immunology often conveys the image of large molecules, either in the soluble state or in the membrane of leukocytes, forming multiple contacts with a target for actions of the immune system. Avidity names the ability of a polyvalent molecule to form multiple connections of the same kind with ligands tethered to the same surface. Polyvalent interactions are vastly stronger than their monovalent equivalent. In the present review, the functional consequences of polyvalent interactions are explored in a perspective of recent theoretical advances in understanding the thermodynamics of such binding. From insights on the structural biology of soluble pattern recognition molecules as well as adhesion molecules in the cell membranes or in their proteolytically shed form, this review documents the prominent role of polyvalent interactions in making the immune system a formidable barrier to microbial infection as well as constituting a significant challenge to the application of nanomedicines. (C) 2012 Elsevier B.V. All rights reserved.

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