Abstract
ISOLATED polypeptide chains of the T-cell antigen receptor complex are degraded or retained in the endoplasmic reticulum (ER)1–4. Assembly of the multisubunit complex allows the individual chains to escape retention in the ER and to be expressed on the cell surface. We engineered a series of deletions in the CD3ɛ subunit of the human T-cell receptor in order to find the sequences responsible for its retention in the ER. Deletion of amino acids 171 to 180 in the cytosolic tail resulted in the cell-surface expression of the isolated chain. This sequence also promotes retention when it is appended to CD4, a plasma membrane protein. Mutagenesis of the 10-amino-acid CD3ɛ sequence established that the tyrosine and serine residues are important for ER retention. This and other ER retention signals must be hidden when a complete T-cell receptor complex is assembled in order to allow its expression on the cell surface.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Ashwell, J. D. & Klausner, R. D. A. Rev. Immun. 8, 139–167 (1990).
Clevers, H. C., Alarcón, B., Wileman, T. E. & Terhorst, C. A. Rev. Immun. 6, 629–662 (1988).
Lippincott-Schwartz, J., Bonifacino, J. S., Yuan, L. C. & Klausner, R. D. Cell 54, 209–220 (1988).
Wileman, T., Carson, G. R., Concino, M., Ahmed, A. & Terhorst, C. J. Cell Biol. 110, 973–986 (1990).
Terasaki, M., Song, J., Wong, J. R., Weiss, M. J. & Chen, L. B. Cell 38, 101–108 (1984).
Weissman, A. M. et al. Proc. natn. Acad Sci. U.S.A. 85, 9709–9713 (1988).
Romeo, C., Amiot, M. & Seed, B. Cell 68, 889–897 (1992).
Reth, M. Nature 338, 383–384 (1989).
Nash, R. A., Scherf, U. & Storb, R. Immunogenetics 33, 396–398 (1991).
Munro, S. & Pelham, H. R. B. Cell 48, 899–907 (1987).
Nilsson, T., Jackson, M. R. & Peterson, P. A. Cell 58, 707–718 (1989).
Letorneur, F. & Klausner, R. D. Science 255, 79–82 (1992).
Bonifacino, J., Cosson, P. Shah, N. & Klausner, R. D. EMBO J. 10, 2783–2793 (1991).
Hall, C. et al. Int. Immun. 3, 359–368 (1991).
Alarcón, B. et al. EMBO J. 10, 903–921 (1991).
Kappes, D. J. & Tonegawa, S. Proc. natn. Acad. Sci. U.S.A. 88, 10619–10623 (1991).
Inouye, S. & Inouye, M. in Directed Mutagenesis (ed. McPherson, M. J.) 71–82 (Oxford University Press, New York, 1991).
Takebe, Y. et al. Molec. cell. Biol. 8, 466–472 (1988).
Blumberg, R. S. et al. Proc. natn. Acad. Sci. U.S.A. 87, 7220–7224 (1990).
Pagano, R. E. Meth. Cell Biol. 29, 75–85 (1989).
Salmerón, A., Sánchez-Madrid, F., Ursa, M. A., Fresno, M. & Alarcón, B. J. Immun. 147, 3047–3052 (1991).
Carrera, A. C., Sánchez-Madrid, F., López-Botet, M., Bernabeu, C. & Landazuri, M. O. Eur. J. Immun. 17, 179–186 (1987).
Alarcón, B., Berkhout, B., Breitmeyer, J. & Terhorst, C. J. biol. Chem. 263, 2953–2961 (1988).
Bonifacino, J. S., Cosson, P. & Klausner, R. D. Cell 63, 503–513 (1990).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mallabiabarrena, A., Fresno, M. & Alarcón, B. An endoplasmic reticulum retention signal in the CD3ɛ chain of the T-cell receptor. Nature 357, 593–596 (1992). https://doi.org/10.1038/357593a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/357593a0
This article is cited by
-
IRAP-dependent endosomal T cell receptor signalling is essential for T cell responses
Nature Communications (2020)
-
LAPTM5 promotes lysosomal degradation of intracellular CD3ζ but not of cell surface CD3ζ
Immunology & Cell Biology (2014)
-
Assembly, organization, and function of the COPII coat
Histochemistry and Cell Biology (2008)
-
Targeting of T Lymphocytes to Melanoma Cells Through Chimeric Anti-GD3 Immunoglobulin T-Cell Receptors
Neoplasia (2000)
-
Independent mutations of the human CD3–ε gene resulting in a T cell receptor/CD3 complex immunodeficiency
Nature Genetics (1993)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
