Homotypic interactions mediated by Ly108 and SLAM control NKT lineage development

• Published in: Immunity (Cambridge, Mass.) Mass.), 2007-11, Vol.27 (5), p.751-762
• Main Authors: Griewank, Klaus, Borowski, Christine, Rietdijk, Svend, Wang, Ninghai, Julien, Aimee, Wei, Datsen G., Mamchak, Alusha A., Terhorst, Cox, Bendelac, Albert
• Format: Article
• Language: English
• ISSN: 1074-7613
• DOI: 10.1016/j.immuni.2007.08.020

Commitment to the T and NKT cell lineages is determined during αβ T cell receptor (TCR)-mediated interactions of common precursors with ligand-expressing cells in the thymus. Whereas mainstream thymocyte precursors recognize Major Histocompatibility Complex (MHC) ligands expressed by stromal cells, NKT precursors interact with CD1d ligands expressed by cortical thymocytes. Here, we demonstrate that such homotypic T-T interactions generate ‘second signals’ mediated by the cooperative engagement of the homophilic receptors Ly108 and SLAM and downstream recruitment of the adaptor SAP and the Src kinase Fyn, which are essential for the lineage expansion and differentiation of the NKT lineage. These receptor interactions are required during TCR engagement and therefore only occur when selecting ligands are presented by thymocytes rather than epithelial cells which do not express Ly108 or SLAM. Thus, the topology of NKT ligand recognition determines the availability of a co-signaling pathway that is essential for NKT lineage development.