Allelic exclusion of the T cell receptor β locus requires the SH2 domain-containing leukocyte protein (SLP)-76 adaptor protein

Iannis Aifantis, Vadim I. Pivniouk, Frank Gärtner, Jacqueline Feinberg, Wojciech Swat, Frederick W. Alt, Harald Von Boehmer, Raif S. Geha

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

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-α/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.

Original languageEnglish
Pages (from-to)1093-1102
Number of pages10
JournalJournal of Experimental Medicine
Volume190
Issue number8
DOIs
StatePublished - Oct 18 1999
Externally publishedYes

Keywords

  • Allelic exclusion
  • Pre-TCR
  • SLP-76
  • TCR signaling
  • Thymocyte development

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