Article: article from journal or magazin.
A critical role for the T cell receptor alpha-chain connecting peptide domain in positive selection of CD1-independent NKT cells.
European Journal of Immunology
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Natural killer T (NKT) cells are a subset of mature alpha beta TCR(+) cells that co-express NK lineage markers. Whereas most NKT cells express a canonical Valpha14/Vbeta8.2 TCR and are selected by CD1d, a minority of NKT cells express a diverse TCR repertoire and develop independently of CD1d. Little is known about the selection requirements of CD1d-independent NKT cells. We show here that NKT cells develop in RAG-deficient mice expressing an MHC class II-restricted transgenic TCR (Valpha2/Vbeta8.1) but only under conditions that lead to negative selection of conventional T cells. Moreover development of NKT cells in these mice is absolutely dependent upon an intact TCR alpha-chain connecting peptide domain, which is required for positive selection of conventional T cells via recruitment of the ERK signaling pathway. Collectively our data demonstrate that NKT cells can develop as a result of high avidity TCR/MHC class II interactions and suggest that common signaling pathways are involved in the positive selection of CD1d-independent NKT cells and conventional T cells.
Animals, Antigens, CD1/immunology, Binding Sites, CD8-Positive T-Lymphocytes/immunology, Hepatocytes, Histocompatibility Antigens Class II/immunology, Immunophenotyping, Killer Cells, Natural/immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Peptides/immunology, Receptors, Antigen, T-Cell, alpha-beta/genetics, Receptors, Antigen, T-Cell, alpha-beta/immunology
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