Published online 3 September 2001. doi:10.1084/jem.194.5.695
© The Rockefeller University Press, 0022-1007/2001/9/695/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 5, September 3, 2001 695-704
The Biological Activity of Natural and Mutant Pt
Alleles
Deena Gibbonsa,
Nataki C. Douglasd,
Domingo F. Barberd,
Qiang Liua,
Renee Sullod,
Liping Gengd,
Hans-Joerg Fehlingc,
Harald von Boehmerb, and
Adrian C. Haydaya,d
a Guy's King's St. Thomas' Medical School, Guy's Hospital, London Bridge, London SE1 9RT, United Kingdom
b Dana Farber Cancer Institute, Boston, MA 02115
c Department of Immunology, Medical Faculty/University Clinics Ulm, D-89070 Ulm, Germany
d Yale University, Department of Molecular, Cell and Developmental Biology, New Haven, CT 06520
Peter Gorer Department of Immunobiology, GKT School of Medicine, King's College, London, 3rd Floor New Guy's House, Guy's Hospital, London SE1 9RT, United Kingdom.44-(0)20-7955-496144-(0)20-7955-8768
adrian.hayday{at}kcl.ac.uk
β selection is a major checkpoint in early thymocyte differentiation, mediated by successful expression of the pre-T cell receptor (TCR) comprising the TCRβ chain, CD3 proteins, and a surrogate TCR
chain, pT. The mechanism of action of the pre-TCR is unresolved. In humans and mice, the pT gene encodes two RNAs, pTa, and a substantially truncated form, pTb. This study shows that both are biologically active in their capacity to rescue multiple thymocyte defects in pT–/– mice. Further active alleles of pT include one that lacks both the major ectodomain and much of the long cytoplasmic tail (which is unique among antigen receptor chains), and another in which the cytoplasmic tail is substituted with the short tail of TCR C. Thus, very little of the pT chain is required for function. These data support a hypothesis that the primary role of pT is to stabilize the pre-TCR, and that much of the conserved structure of pT probably plays a critical regulatory role.
Key Words: pre-TCR • thymocyte development • /β T cells • allelic exlusion • transgenic
D. Gibbons, N.C. Douglas, and D.F. Barber contributed equally to this work.
D.F. Barber's present address is Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
L. Geng's present address is Dana Farber Cancer Institute, Boston, MA 02115.
Q. Liu's present address is Brigham and Women's Hospital, Boston, MA 02115.
© 2001 The Rockefeller University Press
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
-
Navarro, M. N., Nusspaumer, G., Fuentes, P., Gonzalez-Garcia, S., Alcain, J., Toribio, M. L.
(2007). Identification of CMS as a cytosolic adaptor of the human pT{alpha} chain involved in pre-TCR function. Blood
110: 4331-4340
[Abstract]
[Full Text]
-
Erman, B., Guinter, T. I., Singer, A.
(2004). Defined {alpha}{beta} T Cell Receptors with Distinct Ligand Specificities Do Not Require Those Ligands to Signal Double Negative Thymocyte Differentiation. JEM
199: 1719-1724
[Abstract]
[Full Text]
-
Borowski, C., Li, X., Aifantis, I., Gounari, F., von Boehmer, H.
(2004). Pre-TCR{alpha} and TCR{alpha} Are Not Interchangeable Partners of TCR{beta} during T Lymphocyte Development. JEM
199: 607-615
[Abstract]
[Full Text]
-
Haks, M. C., Belkowski, S. M., Ciofani, M., Rhodes, M., Lefebvre, J. M., Trop, S., Hugo, P., Zuniga-Pflucker, J. C., Wiest, D. L.
(2003). Low Activation Threshold As a Mechanism for Ligand-Independent Signaling in Pre-T Cells. J. Immunol.
170: 2853-2861
[Abstract]
[Full Text]
-
Murga, C., Barber, D. F.
(2002). Molecular Mechanisms of Pre-T Cell Receptor-induced Survival. J. Biol. Chem.
277: 39156-39162
[Abstract]
[Full Text]
-
Sasada, T., Touma, M., Chang, H.-C., Clayton, L. K., Wang, J.-h., Reinherz, E. L.
(2002). Involvement of the TCR C{beta} FG Loop in Thymic Selection and T Cell Function. JEM
195: 1419-1431
[Abstract]
[Full Text]
