Pre-TCRα and TCRα are not interchangeable partners of TCRβ during T lymphocyte development

被引:44
作者
Borowski, C [1 ]
Li, XY [1 ]
Aifantis, I [1 ]
Gounari, F [1 ]
von Boehmer, H [1 ]
机构
[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA
关键词
T lymphocyte subsets; cell lineage; receptor-mediated signal transduction; receptor antigen; T-cell gamma delta;
D O I
10.1084/jem.20031973
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In contrast with the alphabeta T cell receptor (TCK), 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 TCRalpha precisely at the pre-TCR checkpoint, at levels resembling those of endogenous pre-TCRalpha (pTalpha), and in the absence of endogenous pTalpha. Both in isolation and more dramatically when in competition with pTalpha, TCRalpha induced defective proliferation, survival, and differentiation of alphabeta T lymphocyte precursors, as well as impaired commitment to the alphabeta T lymphocyte lineage. Substitution of TCRalpha transmembrane and cytoplasmic domains with those of pTalpha generated a hybrid molecule possessing enhanced competitive abilities. We conclude that features intrinsic to the pre-TCR, which are absent in TCRalpha, are essential for its unique function.
引用
收藏
页码:607 / 615
页数:9
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