A class I transgene reveals regulatory events on chromosome 1 marking peripheral T cell differentiation and memory

Cari Roark Sloma, Michael J. Hansen, Audrey A. MacDougall, Virginia P. Van Keulen, Robert B. Jenkins, Larry R. Pease

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

T cells respond to external signals by altering patterns of gene expression. Our characterization of a transgenic mouse revealed a genetic locus that is specifically regulated in T cells. Elucidation of the factors controlling the expression of the marker transgene may reveal basic regulatory mechanisms used by T cells as they differentiate from naive to primed/memory T cells. Although endogenous MHC class I Kq expression is normal in these animals, expression of the Kb transgene differentiates naive from primed/memory T cells. KbHigh T cells bear the phenotypic and functional properties of primed/memory T cells, while KbLow T cells have naive phenotypes. The transition from KbLow to KbHigh appears to involve signals resulting from engagement of the TCR. We show that transgene integration has occurred on chromosome 1, between D1Mit365 and D1Mit191. The gene regulatory mechanisms directing expression of the locus marked by the transgene are distinct from those controlling other known T cell-related genes within this locus. Stimulation of KbHigh T cells results in the up-regulation of both the endogenous Kq gene and the Kb transgene. However, the same stimuli induce increased expression of only Kq on KbLow T cells. This indicates that even though the transcription factors necessary for class I expression are present in KbLow T cells, the Kb gene appears not to be accessible to these factors. These findings suggest a change in chromatin structure at the transgene integration site as cells progress from a naive to a primed/memory differentiation state.

Original languageEnglish (US)
Pages (from-to)7564-7572
Number of pages9
JournalJournal of Immunology
Volume174
Issue number12
DOIs
StatePublished - Jun 15 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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