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The Role of TCR Specificity and Clonal Competition During Reconstruction of the Peripheral T Cell Pool¹

Lymphocyte Population Biology Unit, Centre National de la Recherche Scientifique, Institut Pasteur, Paris, France

Survival of peripheral CD8⁺ T cells requires TCR interactions with peptide-MHC complexes (p-MHC). In the adult mouse, in the presence of homeostatic mechanisms that strictly control T cell numbers, it is likely that diverse T cell clones may compete for shared patterns of p-MHC. In the present study, we investigate whether the recognition of p-MHC overlaps between different T cell populations and what role does this process plays in the establishment of the peripheral T cell pools. Using an experimental strategy that follows the fate of adoptively transferred polyclonal T cells into RAG^0/0 or different TCR transgenic RAG^0/0 hosts, we demonstrate that T cells bearing different TCR specificities share identical TCR-specific requirements for survival and lymphopenia driven proliferation (LDP). This interclonal competition applies to both naive and activated/memory T cells and is partially determined by the clone size of the established/resident T cells. However, clonal competition with activated/memory resident T cells impacts differently on the fate of newly produced bone-marrow-derived T cells or adoptively transferred peripheral T cells. Overall, our findings indicate that p-MHC define multiple diverse resource niches that can be shared by T cells from different compartments.

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¹ C.L. is supported by a grant from the Portuguese Foundation for Science and Technology (FCT) and by a Pasteur-Weizmann grant. This work was supported by the Pasteur Institute, the Centre National de la Recherche Scientifique, and grants from Agence Nationale de Recherches sur le SIDA and Association pour la Recherche sur le Cancer.

² Address correspondence and reprint requests to Dr. Sylvie Garcia, Lymphocyte Population Biology Unit, Institut Pasteur, 25 rue du Dr. Roux, Paris, France. E-mail address: sygarcia{at}pasteur.fr

³ Abbreviations used in this paper: BM, bone marrow; sp-MHC, self-peptide-MHC complex; Tg, transgenic; LDP, lymphopenia driven proliferation; LCMV, lymphocytic choriomeningitis virus; LN, lymph node.

⁴ The online version of this article contains supplemental material.