Dual‐Receptor T Cells Expressing One Self‐Restricted TCR

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Abstract
During thymic development, T cells rearrange and express genes encoding clonotypic T‐cell receptors (TCR), and undergo selective events involving interactions between TCR and thymic major histocompatibility complex (MHC) molecules. Recent studies indicate that up to 30% of peripheral T cells may express two TCR, that both TCR on these cells are functional, and that dual‐specific T cells can promote autoimmunity. Here we demonstrate that dual‐receptor T cells are readily generated in class II‐deficient (class II−) mice expressing the class II‐restricted AND TCR transgene (TCRtg). While this TCRtg is unable to promote positive selection in class II− mice, T cells arise in class II−TCR+tg mice by co‐expressing non‐transgenic endogenous TCR that permit positive selection on class I molecules. Our findings indicate that when a rearranged TCR fails to promote positive selection on self MHC molecules, expression of a second receptor can rescue the developing T cell. Accordingly, many dual‐receptor T cells may actually be mono‐specific in vivo, possessing only one self MHC‐restricted TCR, and therefore should not require unique regulatory controls to prevent autoreactivity.

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