The Journal of Experimental Medicine
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Published online 3 September 2001. doi:10.1084/jem.194.5.695
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© 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

Brief Definitive Report

The Biological Activity of Natural and Mutant Pt{alpha} 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{alpha} chain, pT{alpha}. The mechanism of action of the pre-TCR is unresolved. In humans and mice, the pT{alpha} gene encodes two RNAs, pT{alpha}a, and a substantially truncated form, pT{alpha}b. This study shows that both are biologically active in their capacity to rescue multiple thymocyte defects in pT{alpha}–/– mice. Further active alleles of pT{alpha} 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{alpha}. Thus, very little of the pT{alpha} chain is required for function. These data support a hypothesis that the primary role of pT{alpha} is to stabilize the pre-TCR, and that much of the conserved structure of pT{alpha} probably plays a critical regulatory role.

Key Words: pre-TCR • thymocyte development • {alpha}/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


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