Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 101, Issue 14, Pages 4936-4941Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0401133101
Keywords
microarray; gene expression profile; negative selection
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T cell antigen receptor (TCR) signaling is necessary but not sufficient to promote the positive selection of CD4(+)CD8(+) thymocytes into CD4(+) or CD8(+) mature T cells. Notch signaling has also been implicated as a potential regulator of both CD4/CD8 T cell development and TCR signaling. However, the relationship between positive selection, TCR signaling, and Notch remains unclear. Here we use DNA microarray analysis to compare gene expression changes in CD4(+)CD8(+) double-positive thymocytes undergoing positive selection, TCR stimulation, and Notch activation. We find that the genes induced during positive selection can be resolved into two distinct sets. One set, which we term TCR-induced, is also induced by in vitro TCR stimulation and contains a large proportion of transcription factors. A second set, which we term positive-selection-induced, is not induced by in vitro TCR simulation and contains a large proportion of genes involved in signal transduction pathways. Genes induced by Notch activity overlap substantially with genes induced during positive selection. We also find that Notch activity potentiates the effects of TCR stimulation on gene expression. These results help to identify TCR- and positive-selection-specific transcriptional events and help to clarify the relationship between positive selection and Notch.
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