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CD8⁺ T Lymphocytes in Double TCR Transgenic Mice. II. Competitive Fitness of Dual TCR CD8⁺ T Lymphocytes in the Peripheral Pools¹

Lymphocyte Population Biology Unit, Unité de Recherche Associée, Centre National de la Recherche Scientifique, Institut Pasteur, Paris, France

We studied Rag2-deficient mice bearing two rearranged TCR transgenes, both restricted to the MHC H-2D^b class I molecule. We have previously shown that, in these DTg mice, most peripheral CD8 T cells express one TCR chain associated with two TCR chains, as in one-third of the mature T cells from normal mice. We examined the functional behavior of the dual-receptor CD8 T cells developing either in the absence or in the presence of self-Ag. The dual-receptor CD8 T cells, which develop in absence of self-Ag, show efficient responses to immunization and remain sensitive to induction of peripheral tolerance. In contrast to single TCR T cells, the dual-TCR cells, when tolerized upon exposure to high levels of self-Ag, are not deleted and therefore may exert important regulatory functions. When developing in the presence of self-Ag, the dual-receptor-expressing CD8 T cells escape central deletion, but are not fully competent to respond to cognate stimuli. Overall, we found that the dual-TCR CD8 T cells show a poor competitive value and can be out-competed by single-TCR cells, both in the course of immune responses and in reconstitution experiments. The decreased fitness of the dual-receptor cells may contribute to diminishing the autoimmune hazard that they could represent.

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