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Published online before print January 20, 2005

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(Journal of Leukocyte Biology. 2005;77:830-841.)
© 2005 by Society for Leukocyte Biology

Thymocyte stimulation by anti-TCR-ß, but not by anti-TCR-, leads to induction of developmental transcription program

Nathalie Niederberger^*, Lukas K. Buehler, Jeanette Ampudia^* and Nicholas R. J. Gascoigne^*,1

^* Department of Immunology, IMM1, The Scripps Research Institute, La Jolla, California; and
SciScript, Inc., San Diego, California

¹ Correspondence: Department of Immunology, IMM1, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037. E-mail: gascoigne{at}scripps.edu

Anti-T cell receptor (aTCR) antibody (Ab) stimulation of T cells results in TCR down-modulation and T cell activation. Differences in the effect of anti--chain and ß-chain Ab have been reported on thymocytes. Anti-ß-chain Ab but not anti--chain reagents cause long-term TCR down-modulation. However, both types of Ab result in TCR cross-linking and activate early steps in signal transduction. In this study, we show that TCR internalization and calcium flux, hallmarks of T cell activation, are similar with aV and aVß treatment. Therefore, we have compared the gene expression profiles of preselection thymocytes stimulated with these reagents. We find that aV treatment does not cause any significant change in gene expression compared with control culture conditions. In contrast, aVß stimulation results in numerous changes in gene expression. The alterations of expression of genes known to be expressed in thymocytes are similar to changes caused by positive thymic selection, suggesting that the expression of some of the genes without known roles in thymocyte development and of novel genes whose expression is found to be altered may also be involved in this process.

Key Words: microarray • positive selection • signaling • T cell activation • TCR down-modulation

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