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Science 310 (5752): 1321-1324

Copyright © 2005 by the American Association for the Advancement of Science

Assistance of Microbial Glycolipid Antigen Processing by CD1e

Henri de la Salle,1* Sabrina Mariotti,2* Catherine Angenieux,1* Martine Gilleron,3* Luis-Fernando Garcia-Alles,4 Dag Malm,5 Thomas Berg,6 Samantha Paoletti,2 Blandine Maître,1 Lionel Mourey,4 Jean Salamero,7 Jean Pierre Cazenave,8 Daniel Hanau,1 Lucia Mori,2 Germain Puzo,3{dagger} Gennaro De Libero2{dagger}

Abstract: Complexes between CD1 molecules and self or microbial glycolipids represent important immunogenic ligands for specific subsets of T cells. However, the function of one of the CD1 family members, CD1e, has yet to be determined. Here, we show that the mycobacterial antigens hexamannosylated phosphatidyl-myo-inositols (PIM6) stimulate CD1b-restricted T cells only after partial digestion of the oligomannose moiety by lysosomal {alpha}-mannosidase and that soluble CD1e is required for this processing. Furthermore, recombinant CD1e was able to bind glycolipids and assist in the digestion of PIM6. We propose that, through this form of glycolipid editing, CD1e helps expand the repertoire of glycolipidic T cell antigens to optimize antimicrobial immune responses.

1 INSERM, U725, Etablissement Francais du Sang-Alsace, F-67065 Strasbourg, France.
2 Experimental Immunology, Department of Research, Basel University Hospital, CH-4031 Basel, Switzerland.
3 CNRS, UMR 5089, Immunochimie et Glycoconjugués Mycobacteriens, Institut de Pharmacologie et de Biologie Structurale, F-31077 Toulouse Cedex, France.
4 Biophysique Structurale, Département Mécanismes Moléculaires des Infections Mycobactériennes, Institut de Pharmacologie et de Biologie Structurale, F-31077 Toulouse Cedex, France.
5 Department of Medicine, University Hospital of Northern Norway, N-9038 Tromsø, Norway.
6 Department of Pathology, University Hospital of Northern Norway, N-9038 Tromsø, Norway.
7 CNRS, UMR 144, Institut Curie, F-75005 Paris, France.
8 INSERM, U311, Etablissement Francais du Sang-Alsace, F-67065 Strasbourg, France.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: gennaro.delibero{at} (G.D.L.); germain.puzo{at} (G.P.)

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