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.
|Number of pages||10|
|Journal||Journal of Experimental Medicine|
|State||Published - Oct 18 1999|
- Allelic exclusion
- TCR signaling
- Thymocyte development