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1.1/V
2 
TCR in 
/
Lineage Choice in the Thymus
Max-Planck-Institut für Immunbiologie, Freiburg, Germany
Development of 
and 
T cells depends on productive rearrangement of the appropriate TCR genes and their subsequent expression as proteins. TCR
and TCR
proteins first appear in DN3 and DN4 thymocytes, respectively. So far, it is not clear whether this is due to a delayed expression of TCR
proteins or to a more rapid progression to DN4 of thymocytes expressing TCR
. The answer to this question bears on the distinction between instructive and stochastic models of 
/
lineage decision. To study this question, we first monitored initial TCR protein expression in wild-type and TCR transgenic mice in reaggregate thymic organ cultures. A TCR
transgene was expressed in nearly all DN3 and DN4 cells, accelerated DN3 to DN4 transition, and strongly diminished the number of cells that express TCR
proteins. In contrast, TCR
transgenes were expressed only in a fraction of DN4 cells, did not accelerate DN3 to DN4 transition, and did not reduce the number of DN4 cells expressing TCR
proteins. The TCR
transgene partially inhibited endogenous TCR
rearrangements, whereas the TCR
transgenes did not inhibit endogenous TCR
rearrangements. Second, we analyzed frequencies of productive TCR
and TCR
V(D)J junctions in DN3 and DN4 subsets. Most importantly, frequencies of productive TCR
rearrangements (V
5, V
1.1, and V
2) appeared unselected in DN3. The results suggest a late and restricted expression of the corresponding 
TCR, severely limiting their putative instructional opportunities in 
/
divergence.
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C. E. Busse, A. Krotkova, and K. Eichmann The TCR{beta} Enhancer Is Dispensable for the Expression of Rearranged TCR{beta} Genes in Thymic DN2/DN3 Populations but Not at Later Stages J. Immunol., September 1, 2005; 175(5): 3067 - 3074. [Abstract] [Full Text] [PDF] |
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