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J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/10/1149/10 $2.00
Volume 186, Number 7, October 6, 1997 1149-1158

How Many Thymocytes Audition for Selection?

By Matthias Merkenschlager,* Daniel Graf,* Matthew Lovatt,* Ursula Bommhardt,Dagger Rose Zamoyska,Dagger and Amanda G. Fisher*

From the * Lymphocyte Development Group, Medical Research Council Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 0NN, United Kingdom; and Dagger  Division of Molecular Immunology, National Institute of Medical Research, London, United Kingdom

T cell maturation requires the rearrangement of clonotypic T cell receptors (TCR) capable of interacting with major histocompatibility complex (MHC) ligands to initiate positive and negative selection. Only 3-5% of thymocytes mature to join the peripheral T cell pool. To investigate the basis for this low success rate, we have measured the frequency of preselection thymocytes capable of responding to MHC. As many as one in five MHC-naive thymocytes show upregulation of activation markers on exposure to MHC-expressing thymic stroma in short-term reaggregate culture. The majority of these cells display physiological changes consistent with entry into the selection process within 24 h. By exposing TCR transgenic thymocytes to a range of MHC-peptide complexes, we show that CD69 induction is indicative of thymocyte selection, positive or negative. Our data provide evidence that the fraction of thymocytes that qualify to enter the thymic selection process far exceeds the fraction that successfully complete it, and suggest that most MHC-reactive thymocytes are actively eliminated in the course of selection.


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