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International Immunology, Vol. 11, No. 1, 113-119, January 1999
© 1999 Japanese Society for Immunology

Development and function of autospecific dual TCR+ T lymphocytes

Robin K. Paterson1, Horst Bluethmann2, Pi-ou Tseng3, Anne Dunlap3 and Terri H. Finkel1,3,4

1 Department of Immunology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
2 Central Research Units, F. Hoffmann-LaRoche, 4002 Basel, Switzerland
3 Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA
4 Departments of Pediatrics and Biochemistry & Molecular Genetics, University of Colorado Health Sciences Center, Denver, CO 80262, USA

Correspondence to: R. K. Paterson

Recent studies have challenged the long held concept that each T lymphocyte expresses on its surface only a single, unique {alpha}ßTCR. Dual TCR+ T cells have been recognized, however, their origin and potential to escape screening for self-reactivity remain obscure. We now report the thymic generation of dual {alpha}ßTCR+ T cells in the H-2Db/H-Y-specific TCR transgenic (Tg) mouse. Dual TCR+ thymocytes were positively selected less efficiently than single TCR+ thymocytes, although a subset attained maturity. Importantly, when TCR Tg mice were bred onto a negatively selecting background, auto-specific cells survived central deletion and matured as CD4+ dual TCR+ cells. These cells were autoreactive when CD8 expression was restored. The existence of autospecific, dual TCR+ T cells may have implications for the maintenance of self tolerance.

Keywords: autoreactivity, CD4, CD8, IL-4, TCR, thymic development, thymic selection, thymocytes

Transmitting editor: L. Glimcher


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