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© The Rockefeller University Press, 0022-1007/1999/10/1093/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 8, October 18, 1999 1093-1102

Original Article

Allelic Exclusion of the T Cell Receptor β Locus Requires the Sh2 Domain–Containing Leukocyte Protein (Slp)-76 Adaptor Protein

Iannis Aifantisa, Vadim I. Pivnioukb, Frank Gärtnerc, Jacqueline Feinberga, Wojciech Swatc, Frederick W. Altc, Harald von Boehmera, and Raif S. Gehab

a Institut National de la Santé et Recherche Medicale (INSERM) U373, Hôpital Necker Enfants-Malades, Paris cedex 15, France
b Division of Immunology, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115
c Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115
Enders 8, Div. of Immunology, 300 Longwood Ave., Children's Hospital, Boston, MA 02115.617-355-8205617-355-7603

geha{at}a1.tch.harvard.edu

Signaling via the pre-T cell receptor (TCR) is required for the proliferative expansion and maturation of CD4–CD8– double-negative (DN) thymocytes into CD4+CD8+ double-positive (DP) cells and for TCR-β allelic exclusion. The adaptor protein SH2 domain–containing leukocyte protein (SLP)-76 has been shown to play a crucial role in thymic development, because thymocytes of SLP-76–/– mice are arrested at the CD25+CD44– DN stage. Here we show that SLP-76–/– DN thymocytes express the pre-TCR on their surfaces and that introduction of a TCR-{alpha}/β transgene into the SLP-76–/– background fails to cause expansion of DN thymocytes or developmental progression to the DP stage. Moreover, analysis of TCR-β rearrangement in SLP-76–/– TCR-transgenic mice or in single CD25+CD44– DN cells from SLP-76–/– mice indicates an essential role of SLP-76 in TCR-β allelic exclusion.

Key Words: SLP-76 • allelic exclusion • thymocyte development • pre-TCR • TCR signaling

1used in this paper: DN, double-negative; DP, double-positive; RAG, recombination activating gene; SLP, SH2 domain–containing leukocyte protein; WT, wild-type

I. Aifantis, V. Pivniouk, and F. Gärtner contributed equally to this work.

© 1999 The Rockefeller University Press


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