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Publication : Distinct requirements for CD1d intracellular transport for development of V(alpha)14 iNKT cells.

First Author  Sillé FC Year  2009
Journal  J Immunol Volume  183
Issue  3 Pages  1780-8
PubMed ID  19587020 Mgi Jnum  J:151699
Mgi Id  MGI:4355088 Doi  10.4049/jimmunol.0901354
Citation  Sille FC, et al. (2009) Distinct requirements for CD1d intracellular transport for development of V(alpha)14 iNKT cells. J Immunol 183(3):1780-8
abstractText  The positive selection of V(alpha)14 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 V(alpha)14 iNKT cell precursors at decreased efficiency, caused a delay in their terminal maturation, and did not invoke V(alpha)14iNKT 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 V(alpha)14 iNKT cells by professional APCs, while for peripheral terminal differentiation the intrinsic CD1d sorting motif is dispensable.
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