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This Article Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0901354v1 183/3/1780    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Sillé, F. C.M. Articles by Boes, M. PubMed PubMed Citation Articles by Sillé, F. C.M. Articles by Boes, M.

Distinct Requirements for CD1d Intracellular Transport for Development of V14 iNKT Cells¹

Fenna C.M. Sillé^*,, Mike Boxem, Dave Sprengers^*,, Natacha Veerapen^¶, Gurdyal Besra^¶ and Marianne Boes^*,,2

*Department of Dermatology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Department of Pediatric Immunology, University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, The Netherlands; Department of Developmental Biology, Utrecht University, Utrecht, The Netherlands; Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands; and ^¶School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom

The positive selection of V14 invariant (i)NKT cells in mice requires CD1d-mediated Ag presentation by CD4⁺CD8⁺ thymocytes. Maturation of newly selected iNKT cells continues in the periphery and also involves CD1d expression. CD1d molecules acquire Ags for presentation in endosomal compartments, to which CD1d molecules have access through an intrinsic CD1d-encoded tyrosine motif and by association with the class II MHC chaperone, invariant chain. In this study, we report the generation of mice in which all CD1d is replaced by CD1d-enhanced yellow fluorescent fusion protein (EYFP). CD1d-EYFP molecules are stable, present lipid Ags, and have near normal subcellular distribution. CD1d-EYFP molecules mediated positive selection of V14 iNKT cell precursors at decreased efficiency, caused a delay in their terminal maturation, and did not invoke V14 iNKT cell effector function as wild-type CD1d could. Using these mice, we show that the intrinsic CD1d-encoded sorting motif mediates thymic selection and activation of V14 iNKT cells by professional APCs, while for peripheral terminal differentiation the intrinsic CD1d sorting motif is dispensable.

² Address correspondence and reprint requests to Dr. Marianne Boes, Department of Pediatric Immunology, University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, The Netherlands. E-mail address: mboes{at}umcutrecht.nl

¹ This work was supported by a predoctoral fellowship from the Boehringer Ingelheim Fonds (to F.S.), the Harvard Skin Disease Research Center, NWO-Veni Grant and RO1-AR052810 (to M.B.). G.S.B. acknowledges support from The Medical Research Council, The Wellcome Trust, and James Bardrick in the form of a Personal Research Chair and a Royal Society Wolfson Research Merit Award.