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

Lymphocyte Population Biology Unit, Centre National de la Recherche Scientifique, Institut Pasteur, Paris, France.
The Journal of Immunology (Impact Factor: 4.92). 06/2009; 182(9):5232-9. DOI: 10.4049/jimmunol.0804071
Source: PubMed


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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Available from: Antonio A Freitas, Sep 29, 2015
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    • "Instead, as used here, chimeric mice reconstituted with a mixture of bone marrow cells composed by 90% of cells originating from control mice and by only 10% of cells from the TCR-Tg mice (i.e., OT-I mice) allowed to more closely model the situation where endogenously produced lymphocytes specific for a given antigen represent only a minority of the T cell repertoire. In these chimeric mice, peripheral deletion of Ova-specific CD8+ cells is readily demonstrable (Fig. 7), probably because deleted cells are progressively replaced by polyclonal non-Tg TCR lymphocytes that may display a better fitness in situation of interclonal competition [22], [23]. "
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    • "e.g. [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18]. "
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