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Science 322 (5908): 1705-1710

Copyright © 2008 by the American Association for the Advancement of Science

Regulation of Dendritic Cell Migration by CD74, the MHC Class II-Associated Invariant Chain

Gabrielle Faure-André,1* Pablo Vargas,1,2* Maria-Isabel Yuseff,1 Mélina Heuzé,1 Jheimmy Diaz,1 Danielle Lankar,1 Veronica Steri,1 Jeremy Manry,1 Stéphanie Hugues,1 Fulvia Vascotto,1 Jérôme Boulanger,3 Graça Raposo,3 Maria-Rosa Bono,2,4 Mario Rosemblatt,2,4,5 Matthieu Piel,3{dagger} Ana-Maria Lennon-Duménil1{dagger}

Abstract: Dendritic cells (DCs) sample peripheral tissues of the body in search of antigens to present to T cells. This requires two processes, antigen processing and cell motility, originally thought to occur independently. We found that the major histocompatibility complex II–associated invariant chain (Ii or CD74), a known regulator of antigen processing, negatively regulates DC motility in vivo. By using microfabricated channels to mimic the confined environment of peripheral tissues, we found that wild-type DCs alternate between high and low motility, whereas Ii-deficient cells moved in a faster and more uniform manner. The regulation of cell motility by Ii depended on the actin-based motor protein myosin II. Coupling antigen processing and cell motility may enable DCs to more efficiently detect and process antigens within a defined space.

1 INSERM U653, Institut Curie, 12 rue Lhomond, 75005, Paris, France.
2 Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Santiago, Chile.
3 CNRS UMR144, Institut Curie, 12 rue Lhomond, 75005, Paris, France.
4 Fundación Ciencia para la Vida and Instituto Milenio de Biología Fundamental y Aplicada, Avenida Zañartu 1482, Santiago, Chile.
5 Facultad de Ciencias de la Salud, Universidad Andrés Bello, Avenida Zañartu 1482, Santiago, Chile.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: amlennon{at}curie.fr (A.-M.L.-D.) and mpiel{at}curie.fr (M.P.)

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