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.