Tcr Revision Is Not Limited To Tcr Tg Mice

While using TCR Tg mice has the obvious benefits of creating an artificial situation in which a uniformly expressed TCR is known to interact with a given self antigen and in which the TCR expression history is known for T cells that can be physically tracked, this artificiality brings with it a set of caveats. It is therefore important to stress that TCR revision is not limited to ectopic, multicopy transgene-encoded receptors. Work from the Kanagawa lab demonstrates that TCR revision in response to recognition of exogenous superantigen can occur within the normally configured TCR-p locus.26 Furthermore, it has been shown recently that in Mtv-8+ Vp5 nontransgenic GFP Tg RAG reporter mice thymectomized at least 4 weeks previously, a significantly greater proportion of Vp5+ cells are GFP+ relative to Vp5- or Vp8+ cells (our unpublished observations). These findings indicate that Mtv-8-driven RAG-mediated TCR revision occurs even in TCR nontransgenic mice. The appearance of CD4+TCRlowRAG+ T cells in normal humans also suggests that TCR revision occurs in individuals carrying normal TCR loci. Thus, the notion that a weak tolerogen can initiate TCR revision appears to be generalizeable to unmanipulated individuals. However, it should not be inferred from these studies that TCR revision is a common response to tolerogen encounter in the lymphoid periphery. Outside of the Vp5+CD4+ population of mature T cells, the frequency of GFP+ T cells in the RAG reporter mice is very low (less than 2%, our unpublished observations). TCR revision may be initiated within a narrow window defined by TCR/superantigen affinity, superantigen expression levels, or frequency of encounter between T cells and superantigen-expressing cells.

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