The role of TCR specificity and clonal competition during reconstruction of the peripheral T cell pool.
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.
Leitão
Catarina
C
Lymphocyte Population Biology Unit, Centre National de la Recherche Scientifique, Institut Pasteur, Paris, France.
Freitas
António A
AA
Garcia
Sylvie
S
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D016654:Genes, RAG-1; D018398:Homeodomain Proteins / Q000235:genetics; D006706:Homeostasis / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D008231:Lymphopenia / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation
D018984:Epitopes, T-Lymphocyte; D018398:Homeodomain Proteins; D011948:Receptors, Antigen, T-Cell; C064658:RAG-1 protein