Pre-TCRα and TCRα Are Not Interchangeable Partners of TCRβ during T Lymphocyte Development

In contrast with the αβ T cell receptor (TCR), the pre-TCR spontaneously segregates to membrane rafts from where it signals in a cell-autonomous fashion. The disparate behaviors of these two receptors may stem either from differences inherent to the distinct developmental stages during which they are expressed, or from features intrinsic and unique to the receptor components themselves. Here, we express TCRα precisely at the pre-TCR checkpoint, at levels resembling those of endogenous pre-TCRα (pTα), and in the absence of endogenous pTα. Both in isolation and more dramatically when in competition with pTα, TCRα induced defective proliferation, survival, and differentiation of αβ T lymphocyte precursors, as well as impaired commitment to the αβ T lymphocyte lineage. Substitution of TCRα transmembrane and cytoplasmic domains with those of pTα generated a hybrid molecule possessing enhanced competitive abilities. We conclude that features intrinsic to the pre-TCR, which are absent in TCRα, are essential for its unique function.