Ligand-dependent inhibition of CD1d-restricted NKT cell development in mice transgenic for the activating receptor Ly49D.

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Serval ID
serval:BIB_A09A6B9B87FD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Ligand-dependent inhibition of CD1d-restricted NKT cell development in mice transgenic for the activating receptor Ly49D.
Journal
Journal of Experimental Medicine
Author(s)
Voyle R.B., Beermann F., Lees R.K., Schümann J., Zimmer J., Held W., MacDonald H.R.
ISSN
0022-1007
Publication state
Published
Issued date
2003
Peer-reviewed
Oui
Volume
197
Number
7
Pages
919-925
Language
english
Notes
Publication types: Journal Article
Abstract
In addition to their CD1d-restricted T cell receptor (TCR), natural killer T (NKT) cells express various receptors normally associated with NK cells thought to act, in part, as modulators of TCR signaling. Immunoreceptor-tyrosine activation (ITAM) and inhibition (ITIM) motifs associated with NK receptors may augment or attenuate perceived TCR signals respectively, potentially influencing NKT cell development and function. ITIM-containing Ly49 family receptors expressed by NKT cells are proposed to play a role in their development and function. We have produced mice transgenic for the ITAM-associated Ly49D and ITIM-containing Ly49A receptors and their common ligand H2-Dd to determine the importance of these signaling interplays in NKT cell development. Ly49D/H2-Dd transgenic mice had selectively and severely reduced numbers of thymic and peripheral NKT cells, whereas both ligand and Ly49D transgenics had normal numbers of NKT cells. CD1d tetramer staining revealed a blockade of NKT cell development at an early precursor stage. Coexpression of a Ly49A transgene partially rescued NKT cell development in Ly49D/H2-Dd transgenics, presumably due to attenuation of ITAM signaling. Thus, Ly49D-induced ITAM signaling is incompatible with the early development of cells expressing semi-invariant CD1d-restricted TCRs and appropriately harmonized ITIM-ITAM signaling is likely to play an important role in the developmental program of NKT cells.
Keywords
Adaptor Proteins, Signal Transducing, Amino Acid Motifs, Animals, Antigens, CD1, Antigens, CD1d, Antigens, Ly, H-2 Antigens, Killer Cells, Natural, Lectins, C-Type, Ligands, Membrane Proteins, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, NK Cell Lectin-Like Receptor Subfamily A, Receptors, Antigen, T-Cell, alpha-beta, Receptors, Immunologic, Receptors, NK Cell Lectin-Like
Pubmed
Web of science
Open Access
Yes
Create date
17/01/2008 15:24
Last modification date
20/08/2019 15:06
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