TY - JOUR
T1 - Pre-TCRα and TCRα Are Not Interchangeable Partners of TCRβ during T Lymphocyte Development
AU - Borowski, Christine
AU - Li, Xiaoyan
AU - Aifantis, Iannis
AU - Gounari, Fotini
AU - Von Boehmer, Harald
PY - 2004/3/1
Y1 - 2004/3/1
N2 - 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.
AB - 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.
KW - Cell lineage
KW - Receptor antigen
KW - Receptor-mediated signal transduction
KW - T lymphocyte subsets
KW - T-cell γδ
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U2 - 10.1084/jem.20031973
DO - 10.1084/jem.20031973
M3 - Article
C2 - 14993248
AN - SCOPUS:1542373531
SN - 0022-1007
VL - 199
SP - 607
EP - 615
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 5
ER -