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

Journal Article

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 CD8(III) 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.

Full Text

Duke Authors

Cited Authors

  • Sarafova, SD; Erman, B; Yu, Q; Van Laethem, F; Guinter, T; Sharrow, SO; Feigenbaum, L; Wildt, KF; Ellmeier, W; Singer, A

Published Date

  • July 2005

Published In

Volume / Issue

  • 23 / 1

Start / End Page

  • 75 - 87

PubMed ID

  • 16039581

International Standard Serial Number (ISSN)

  • 1074-7613

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2005.05.011

Language

  • eng

Conference Location

  • United States