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PMID: 7925292 Published · ppublish English Journal Article

Developmental regulation of alpha beta T cell antigen receptor expression results from differential stability of nascent TCR alpha proteins within the endoplasmic reticulum of immature and mature T cells.

The EMBO journal ·Vol. 13 ·No. 19 ·1994-10-03 ·Pages 4504-14

Kearse KP, Roberts JL, Munitz TI, Wiest DL, Nakayama T, Singer A

Abstract

The alpha beta T cell antigen receptor (TCR) that is expressed on most T lymphocytes is a multisubunit transmembrane complex composed of at least six different proteins (alpha, beta, gamma, delta, epsilon and zeta) that are assembled in the endoplasmic reticulum (ER) and then transported to the plasma membrane. Expression of the TCR complex is quantitatively regulated during T cell development, with immature CD4+CD8+ thymocytes expressing only 10% of the number of surface alpha beta TCR complexes that are expressed on mature T cells. However, the molecular basis for low TCR expression in developing alpha beta T cells is unknown. In the present study we report the unexpected finding that assembly of nascent component chains into complete TCR alpha beta complexes is severely impaired in immature CD4+CD8+ thymocytes relative to their mature T cell progeny. In particular, the initial association of TCR alpha with TCR beta proteins, which occurs relatively efficiently in mature T cells, is markedly inefficient in immature CD4+CD8+ thymocytes, even for a matched pair of transgenic TCR alpha and TCR beta proteins. Inefficient formation of TCR alpha beta heterodimers in immature CD4+CD8+ thymocytes was found to result from the unique instability of nascent TCR alpha proteins within the ER of immature CD4+CD8+ thymocytes, with nascent TCR alpha proteins having a median survival time of only 15 min in CD4+CD8+ thymocytes, but > 75 min in mature T cells. Thus, these data demonstrate that stability of TCR alpha proteins within the ER is developmentally regulated and provide a molecular basis for quantitative differences in alpha beta TCR expression on immature and mature T cells. In addition, these results provide the first example of a receptor complex whose expression is quantitatively regulated during development by post-translational limitations on receptor assembly.

MeSH Terms
Animals Biological Transport/immunology CD4-Positive T-Lymphocytes/immunology CD8-Positive T-Lymphocytes/immunology Cell Differentiation/immunology Endoplasmic Reticulum/immunology Gene Expression Regulation, Developmental/physiology Mice Mice, Inbred C57BL Mice, Transgenic Receptors, Antigen, T-Cell, alpha-beta/biosynthesis,metabolism Spleen/cytology T-Lymphocytes/immunology,physiology Thymus Gland/cytology
Chemicals
Receptors, Antigen, T-Cell, alpha-beta
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Kearse K P
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Roberts J L
Munitz T I
Wiest D L
Nakayama T
Singer A
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1994-10-03
Pages
4504-14
Language
English
Region
England
NLM ID
8208664
PMCID
PMC395383
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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