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 Citations (Scopus)

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

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src Homology Domains
T-Cell Antigen Receptor
Leukocytes
Thymocytes
Proteins
Transgenes
Transgenic Mice

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

Allelic exclusion of the T cell receptor β locus requires the SH2 domain-containing leukocyte protein (SLP)-76 adaptor protein. / Aifantis, Iannis; Pivniouk, Vadim I; Gärtner, Frank; Feinberg, Jacqueline; Swat, Wojciech; Alt, Frederick W.; Von Boehmer, Harald; Geha, Raif S.

In: Journal of Experimental Medicine, Vol. 190, No. 8, 18.10.1999, p. 1093-1102.

Research output: Contribution to journalArticle

Aifantis, Iannis ; Pivniouk, Vadim I ; Gärtner, Frank ; Feinberg, Jacqueline ; Swat, Wojciech ; Alt, Frederick W. ; Von Boehmer, Harald ; Geha, Raif S. / Allelic exclusion of the T cell receptor β locus requires the SH2 domain-containing leukocyte protein (SLP)-76 adaptor protein. In: Journal of Experimental Medicine. 1999 ; Vol. 190, No. 8. pp. 1093-1102.
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