title   
  

Modulation of coreceptor transcription during positive selection dictates lineage fate independently of TCR/coreceptor specificity

Sarafova, Sophia D. and Erman, Batu and Yu, Qing and Van Laethem, François and Guinter, Terry and Sharrow, Susan O. and Feigenbaum, Lionel and Wildt, Kathryn F. and Ellmeier, Wilfried and Singer, Alfred (2005) Modulation of coreceptor transcription during positive selection dictates lineage fate independently of TCR/coreceptor specificity. Immunity, 23 (1). pp. 75-87. ISSN 1074-7613

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Official URL: http://dx.doi.org/10.1016/j.immuni.2005.05.011

Abstract

For developing T cells, coreceptor choice is matched to T cell antigen receptor (TCR) MHC specificity during positive selection in the thymus, but the mechanism remains uncertain. Here, we document that TCR-mediated positive selection signals inactivate the immature CD8III enhancer in double positive (DP) thymocytes, explaining in part the cessation of CD8 coreceptor transcription that occurs during positive selection. More importantly, by placing CD4 protein expression under the control of CD8 transcriptional regulatory elements, we demonstrate that cessation of CD4 coreceptor transcription during positive selection results in precisely the same lineage fate as cessation of CD8 coreceptor transcription. That is, MHC-II-signaled DP thymocytes differentiated into CD8-lineage cytotoxic T cells, despite the MHC-II specificity and CD4 dependence of their TCRs. This study demonstrates that termination of coreceptor transcription during positive selection promotes CD8-lineage fate, regardless of TCR specificity or coreceptor protein identity.

Item Type:Article
Subjects:Q Science > QR Microbiology
ID Code:575
Deposited By:Batu Erman
Deposited On:11 Oct 2005 03:00
Last Modified:25 May 2011 14:02

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