A critical role for the T cell receptor alpha-chain connecting peptide domain in positive selection of CD1-independent NKT cells

Eur J Immunol. 2001 Jun;31(6):1867-75. doi: 10.1002/1521-4141(200106)31:6<1867::aid-immu1867>3.0.co;2-b.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*


  • Antigens, CD1
  • Histocompatibility Antigens Class II
  • Peptides
  • Receptors, Antigen, T-Cell, alpha-beta