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
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    • "Division of T cells in the periphery is determined by competition for stimuli from self-peptides, presented in association with MHC class I (for CD8 þ T cells) and class II (for CD4 þ T cells), found on antigen presenting cells in the lymph nodes, and by soluble factors including IL-7 for naive T cells and IL-15 for memory T cells. Emerging from the thymus with a pattern of recognition of self pMHC that enabled it to survive positive and negative selection, each TCR clonotype is a species that competes for " space " or " niche " in the periphery (DeBoer and Perelson, 1997;Tanchot et al., 1997;Goldrath and Bevan, 1999;Jameson, 2002;Troy and Shen, 2003;Hataye et al., 2006;Moon et al., 2007;Agenes et al., 2008;Leitao et al., 2009). Competition between cells of the same clonotype has been demonstrated by transfer of T cells to TCR transgenic hosts of differing or identical clonotype (Hataye et al., 2006;Min et al., 2004). "
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