Allelic Exclusion of the T Cell Receptor {beta} Locus Requires the SH2 Domain-containing Leukocyte Protein (SLP)-76 Adaptor Protein

doi:10.1084/jem.190.8.1093

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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

Allelic Exclusion of the T Cell Receptor ß Locus Requires the SH2 Domain–containing Leukocyte Protein (SLP)-76 Adaptor Protein

Iannis Aifantis^a, Vadim I. Pivniouk^b, Frank Gärtner^c, Jacqueline Feinberg^a, Wojciech Swat^c, Frederick W. Alt^c, Harald von Boehmer^a, and Raif S. Geha^b
^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

Correspondence to: Raif S. Geha, Enders 8, Div. of Immunology, 300 Longwood Ave., Children's Hospital, Boston, MA 02115. Tel:617-355-7603 Fax:617-355-8205 E-mail:geha{at}a1.tch.harvard.edu.

Signaling via the pre-T cell receptor (TCR) is required forthe proliferative expansion and maturation of CD4^-CD8^- double-negative(DN) thymocytes into CD4⁺CD8⁺ double-positive (DP) cells andfor TCR-ß allelic exclusion. The adaptor protein SH2 domain–containingleukocyte protein (SLP)-76 has been shown to play a crucialrole in thymic development, because thymocytes of SLP-76^-/-mice are arrested at the CD25⁺CD44^- DN stage. Here we show thatSLP-76^-/- DN thymocytes express the pre-TCR on their surfacesand that introduction of a TCR- ${alpha}$ /ß transgene into the SLP-76^-/-background fails to cause expansion of DN thymocytes or developmentalprogression to the DP stage. Moreover, analysis of TCR-ßrearrangement in SLP-76^-/- TCR-transgenic mice or in singleCD25⁺CD44^- DN cells from SLP-76^-/- mice indicates an essentialrole of SLP-76 in TCR-ß allelic exclusion.

Key Words: SLP-76, allelic exclusion, thymocyte development, pre-TCR, TCRsignaling

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