Upregulation of CD4 expression during MHC class II-specific positive selection is essential for error-free lineage choice.

Journal Article

The lineage fate of developing thymocytes is determined by the persistence or cessation of T cell receptor (TCR) signaling during positive selection, with persistent TCR signaling required for CD4 lineage choice. We show here that transcriptional upregulation of CD4 expression is essential for error-free lineage choice during major histocompatibility complex class II (MHC II)-specific positive selection and is critical for error-free lineage choice in TCR-transgenic mice whose thymocytes compete for the identical selecting ligand. CD4 upregulation occurred for endogenously encoded CD4 coreceptors, but CD4 transgenes were downregulated during positive selection, disrupting MHC II-specific TCR signaling and causing lineage errors regardless of the absolute number or signaling strength of transgenic CD4 proteins. Thus, the kinetics of CD4 coreceptor expression during MHC II-specific positive selection determines the integrity of CD4 lineage choice, revealing an elegant symmetry between coreceptor kinetics and lineage choice.

Full Text

Duke Authors

Cited Authors

  • Sarafova, SD; Van Laethem, F; Adoro, S; Guinter, T; Sharrow, SO; Feigenbaum, L; Singer, A

Published Date

  • September 18, 2009

Published In

Volume / Issue

  • 31 / 3

Start / End Page

  • 480 - 490

PubMed ID

  • 19747858

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2009.07.006

Language

  • eng

Conference Location

  • United States