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

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.