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

Roger B. Voyle, Friedrich Beermann, Rosemary K. Lees, Jens Schümann, Jacques Zimmer, Werner Held, H. Robson MacDonald*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

40 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)919-925
Number of pages7
JournalJournal of Experimental Medicine
Issue number7
Publication statusPublished - Apr 2003
Externally publishedYes


  • ITAM-containing receptors
  • ITIM-containing receptors
  • NK receptor repertoire
  • NKT cell development
  • TCR repertoire


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