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Department of Immunology, University of Washington, Seattle, Washington 98195
After developing in the thymus, recent thymic emigrants (RTEs) enter the lymphoid periphery and undergo a maturation process as they transition into the mature naive (MN) T cell compartment. This maturation presumably shapes RTEs into a pool of T cells best fit to function robustly in the periphery without causing autoimmunity; however, the mechanism and consequences of this maturation process remain unknown. Using a transgenic mouse system that specifically labels RTEs, we tested the influence of MHC molecules, key drivers of intrathymic T cell selection and naive peripheral T cell homeostasis, in shaping the RTE pool in the lymphoid periphery. We found that the TCRs expressed by RTEs are skewed to longer CDR3 regions compared with those of MN T cells, suggesting that MHC does streamline the TCR repertoire of T cells as they transition from the RTE to the MN T cell stage. This conclusion is borne out in studies in which the representation of individual TCRs was followed as a function of time since thymic egress. Surprisingly, we found that MHC is dispensable for the phenotypic and functional maturation of RTEs.
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1 The content is solely the responsibility of the authors and does not necessarily represent the official views of either the National Institutes of Health or the National Cancer Institute.
2 This work was supported by grants from the National Cancer Institute (T32CA0095) (to E.G.H.) and the National Institutes of Health (R01 AI 064318) (to P.J.F.).
3 Address correspondence and reprint requests to Dr. Pamela Fink, University of Washington, I-607 H Health Sciences Building, 1959 NE Pacific Street, Box 357650, Seattle, WA 98195. E-mail address: pfink{at}u.washington.edu
4 Abbreviations used in this paper: RTE, recent thymic emigrant; MN, mature naive; Tg, transgenic; RAG2p-GFP Tg, mice transgenic for GFP under control of the RAG2 promoter; SP, single positive; LIP, lymphopenia-induced proliferation.
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