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International Immunology, Vol. 13, No. 8, 1031-1042, August 2001
© 2001 Japanese Society for Immunology

Expression and selection of productively rearranged TCRß VDJ genes are sequentially regulated by CD3 signaling in the development of NK1.1+ {alpha}ß T cells

Nicole Baur, Gabi Nerz, Ahmed Nil and Klaus Eichmann

Max-Planck-Institut für Immunbiologie, Stübeweg 51, 79108 Freiburg, Germany

Correspondence to: K. Eichmann

The generation of thymic NK1.1+{alpha}ßT (NKT) cells involves positive selection of cells enriched for V{alpha}14/Vß8 TCR by CD1d MHC class I molecules. However, it has not been determined whether positive selection is preceded by pre-TCR-dependent ß selection. Here we studied NKT cell development in CD3 signaling-deficient mice (CD3{zeta}/{eta}–/– and/or p56lck–/–) and TCR{alpha}-deficient mice. In contrast to wild-type mice, NK1.1+ thymocytes in CD3 signaling-deficient mice are ~10-fold reduced in number, do not exhibit V{alpha}14–J{alpha}281 rearrangements and fail to express {alpha}ßTCR at the cell surface. However, they exhibit TCRß VDJ rearrangements and pre-T{alpha} mRNA, suggesting that they contain pre-NKT cells. Strikingly, pre-NKT cells of CD3{zeta}/Lck double-deficient mice fail to express TCRß mRNA and protein. Whereas in wild-type NKT cells TCRß VDJ junctions are selected for productive Vß8 and against productive Vß5 rearrangements, Vß8 and Vß5 rearrangements are non-selected in pre-NKT cells of CD3 signaling-deficient mice. Thus, pre-NKT cell development in CD3 signaling-deficient mice is blocked after rearrangement of TCRß VDJ genes but before expression of TCRß proteins. Most NKT cells of TCR{alpha}-deficient mice exhibit cell surface {gamma}{delta}TCR. In contrast to pre-NKT cells of CD3 signaling-deficient mice, ~25% of NKT cells of TCR{alpha}-deficient mice exhibit intracellular TCRß polypeptide chains. Moreover, both Vß8 and Vß5 families are selected for in-frame VDJ joints in the TCRß+ NKT cell subset of TCR{alpha}-deficient mice. The data suggest that CD3 signals regulate initial TCRß VDJ gene expression prior to ß selection in developing pre-NKT cells.

Keywords: CD3 complex, NKT cells, TCRß gene expression, TCRß gene rearrangement, thymus

Transmitting editor: S. H. E. Kaufmann


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