Allelic Exclusion of the T Cell Receptor β Locus Requires the Sh2 Domain–Containing Leukocyte Protein (Slp)-76 Adaptor Protein
Open Access
- 18 October 1999
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 190 (8) , 1093-1102
- https://doi.org/10.1084/jem.190.8.1093
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.Keywords
This publication has 51 references indexed in Scilit:
- Early T Cell Receptor β Gene Expression Is Regulated by the Pre-T Cell Receptor–CD3 ComplexThe Journal of Experimental Medicine, 1999
- Recent developments in lymphocyte activation: linking kinases to downstream signaling eventsJournal of Clinical Investigation, 1999
- Assembly of Productive T Cell Receptor δ Variable Region Genes Exhibits Allelic InclusionThe Journal of Experimental Medicine, 1998
- The CD3-γδε and CD3-ζ/η Modules Are Each Essential for Allelic Exclusion at the T Cell Receptor β Locus but Are Both Dispensable for the Initiation of V to (D)J Recombination at the T Cell Receptor–β, –γ, and –δ LociThe Journal of Experimental Medicine, 1998
- Allelic Exclusion in pTα-deficient Mice: No Evidence for Cell Surface Expression of Two T Cell Receptor (TCR)-β Chains, but Less Efficient Inhibition of Endogeneous Vβ→ (D)Jβ Rearrangements in the Presence of a Functional TCR-β TransgeneThe Journal of Experimental Medicine, 1997
- STRUCTURE AND FUNCTION OF THE PRE-T CELL RECEPTORAnnual Review of Immunology, 1997
- αβ T Cell Development Is Abolished in Mice Lacking Both Lck and Fyn Protein Tyrosine KinasesImmunity, 1996
- Regulation of TCR α and β gene allelic exclusion during T-cell developmentImmunology Today, 1992
- Induction by Antigen of Intrathymic Apoptosis of CD4 + CD8 + TCR lo Thymocytes in VivoScience, 1990
- Identification of a diversity segment of human T-cell receptor β-chain, and comparison with the analogous murine elementNature, 1984