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J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/02/707/10 $2.00
Volume 185, Number 4, February 17, 1997 707-716

The Single Positive T Cells Found in CD3-zeta /eta minus /minus Mice Overtly React with Self-Major Histocompatibility Complex Molecules upon Restoration of Normal Surface Density of T Cell Receptor-CD3 Complex

By Shih-Yao Lin, Laurence Ardouin, Anne Gillet, Marie Malissen, and Bernard Malissen

From the Centre d'Immunologie Institut National de la Santè et de la Recherche Mèdicale-Centre National de Recherche Scientifique de Marseille-Luminy, 13288 Marseille Cedex 9, France

CD3-zeta /eta -deficient mice have small thymuses containing cells that show a profound reduction in the surface levels of T cell receptors and terminate their differentiation at the CD4+CD8+ stage. Rather unexpectedly, CD3- or very low single positive T cells accumulate over time in the spleen and lymph nodes of CD3-zeta /eta -deficient mice after a process dependent on MHC expression. Fusion of these peripheral T cells with a CD3-zeta -positive derivative of the BW5147 TCR-alpha -/beta - thymoma resulted in hybridomas that do express an heterogeneous set of T cell receptor alpha /beta dimers at their surface and at density comparable to those found in hybridomas derived from wild-type peripheral T cells. We have investigated the specificities of these T cell receptors using spleen cells from congenic and mutant mouse strains, and showed that the majority of them readily recognized self-MHC class I or class II molecules. These results demonstrate that by increasing the density and/or output of the T cell receptors expressed in peripheral T cells, one can confer them with the capacity to respond to normal density of self-MHC molecules.


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