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International Immunology Advance Access published online on October 9, 2009
International Immunology, doi:10.1093/intimm/dxp098
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Expression of fully assembled TCR–CD3 complex on double positive thymocytes: synergistic role for the PRS and ER retention motifs in the intra-cytoplasmic tail of CD3{varepsilon}

Jean-Francois Brodeur1,2,*, Samantha Li1,2,*, Ousama Damlaj1 and Vibhuti P. Dave1,2,3

1 Lymphocyte Development Laboratory, Institut de Recherches Cliniques de Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7
2 Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada
3 Department of Medicine, University of Montreal, Montreal, Quebec, Canada

Correspondence to: V. P. Dave; E-mail: vibhuti.dave{at}ircm.qc.ca

TCR expression on double-positive (DP) thymocytes is a prerequisite for thymic selection that results in the generation of mature CD4+ and CD8+ single-positive T cells. TCR is expressed at very low level on preselection DP thymocytes and is dramatically up-regulated on positively selected thymocytes. However, mechanism governing TCR expression on developing thymocytes is not understood. In the present report, we demonstrate that the intra-cytoplasmic (IC) domain of CD3{varepsilon} plays a critical role in regulating TCR expression on DP thymocytes. We provide genetic and biochemical evidence to show that the CD3{varepsilon} IC domain mutations result in elevated expression of fully assembled TCR on DP thymocytes. We also demonstrate that TCR up-regulation on DP thymocytes in these transgenic mice occurs in a ligand-independent manner. Further, we show that the proline-rich sequence and endoplasmic reticulum (ER) retention motifs in the IC domain of CD3{varepsilon} play synergistic role in regulating TCR surface expression on DP thymocytes.

Keywords: CD3, TCR expression, thymocyte development

* These authors contributed equally to this study.

Transmitting editor: A. Singer

Received 13 February 2009, accepted 9 September 2009.


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