With Superantigens But Not Conventional Antigens

In recently published experiments, Huang et al26 initiated RAG expression and TCR-a chain revision in TCR Tg animals injected with spleen cells expressing a viral superantigen (Mtv-6) capable of interacting with the transgenic TCR.26 Similar to the Vp5/Mtv-8 system described above, this TCR revision resulted in the gradual appearance of CD4+ T cells no longer expressing the transgenic TCR, although in these mice, expression of the TCR-a chain, rather than the TCR-p chain, was gradually lost. Although this distinction is likely due to the configuration of the TCR loci in these engineered mice (the TCR-a transgene was incorporated within the endogenous TCR-a locus and subsequent rearrangement events would thereby physically eliminate the TCR-a and not the p transgene), it does emphasize that revision at both the TCR-a and -p loci is possible. It is still unclear whether both genetic regions are equally accessible to the recombinase. Interestingly, Kanagawa and coworkers failed to induce TCR revision in these same animals immunized not with Mtv-6+ cells, but with cells expressing cytochrome c, the foreign antigen recognized in the context of self MHC by the transgenic TCR-apmolecules.26 These striking results remain to be generalized by data from other conventional antigen/ superantigen systems, but they may point to distinct biological outcomes resulting from recognition of these two classes of antigens. It is unclear whether these

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