The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/2/707/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 4, February 17, 1997 707-716

Articles

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

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}–/β– thymoma resulted in hybridomas that do express an heterogeneous set of T cell receptor {alpha}/β 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.

Address correspondence to Bernard Malissen, Centre d'Immunologie INSERM-CNRS de MarseilleLuminy, Case 906, 13288 Marseille Cedex 9, France.


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