An orderly inactivation of intracellular retention signals controls surface expression of the T cell antigen receptor

doi:10.1084/jem.20041133

Published 22 February 2005. doi:10.1084/jem.20041133
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 4, 555-566

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ARTICLE

An orderly inactivation of intracellular retention signals controls surface expression of the T cell antigen receptor

Pilar Delgado and Balbino Alarcón

Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid 28049, Spain

CORRESPONDENCE Balbino Alarcón: Balarcon{at}cbm.uam.es

Exit from the endoplasmic reticulum (ER) is an important checkpointfor proper assembly of multimeric plasma membrane receptors.The six subunits of the T cell receptor (TCR; TCR ${alpha}$ , TCRß,CD3 ${gamma}$ , CD3 ${delta}$ , CD3 ${varepsilon}$ , and CD3 ${zeta}$ ) are each endowed with ER retention/retrievalsignals, and regulation of its targeting to the plasma membraneis therefore especially intriguing. We have studied the importanceof the distinct ER retention signals at different stages ofTCR intracellular assembly. To this end, we have characterizedfirst the presence of ER retention signals in CD3 ${gamma}$ . Despite thepresence of multiple ER retention signals in CD3 ${gamma}$ , ${varepsilon}$ ${gamma}$ dimers reachthe cell surface when the single CD3 ${varepsilon}$ ER retention signal isdeleted. Furthermore, inclusion of this CD3 ${varepsilon}$ mutant promotedplasma membrane expression of incomplete ${alpha}$ ß ${gamma}$ ${varepsilon}$ and ${alpha}$ ß ${delta}$ ${varepsilon}$ complexes without CD3 ${zeta}$ . It therefore appears that the CD3 ${varepsilon}$ ERretention signal is dominant and that it is only overriddenupon the incorporation of CD3 ${zeta}$ . We propose that the stepwiseassembly of the TCR complex guarantees that all assembly intermediateshave at least one functional ER retention signal and that onlya full signaling-competent TCR complex is expressed on the cellsurface.

Abbreviation used: MFI, mean fluorescence intensity.

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