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In This Issue, The Journal of Immunology, Volume 183, Issue 11, December 2009, Pages 6857–6858, https://doi.org/10.4049/jimmunol.0990100
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Periphery Shapes TCR Repertoire
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Following thymic development, T cells enter the peripheral lymphoid compartment where they undergo further phenotypic and functional maturation before attaining the mature “naive” (MN) T cell stage. Whether the TCR repertoire of these recent thymic emigrants (RTEs) is fixed or undergoes further MHC-directed selection in the periphery is unknown. To address this issue, Houston Jr. and Fink (p. 7244) used a transgenic (Tg) mouse system, RAG2p-GFP Tg, to specifically express GFP on RTEs, thus facilitating their identification and isolation. Comparison of both CD4+ and CD8+ RTEs with comparable MN subsets revealed a skewing of longer CDR3 regions in RTEs, suggesting that MHC-driven modulation of the RTE TCR repertoire had occurred. Temporal analysis of maturing RTE TCR repertoires in competitive bone marrow (BM) chimeras, established from a mixture of syngeneic polyclonal TCR and TCR Tg BM cells, confirmed that the RTE TCR repertoire changed during the RTE to MN transition. Surprisingly, when RTE phenotypic and functional maturation were evaluated in mice that were either wholly or peripherally deficient in MHC II expression, both were found to be normal. These data show that the T cell repertoire is still under selective pressure after exiting the thymus, as peripheral MHC expression continues to shape the repertoire of maturing RTEs.