title: Competition for antigen determines the stability of T cell-dendritic cell interactions during clonal expansion.
abstract: The regulation of T cell-dendritic cell (DC) contacts during clonal expansion is poorly defined. Although optimal CD4 T cell responses require prolonged exposure to antigen (Ag), it is believed that stable T cell-DC interactions occur only during the first day of the activation process. Here we show that recently activated CD4 T cells are in fact fully competent for establishing contact with Ag-bearing DC. Using two-photon imaging, we found that whereas prolonged interactions between activated T cells and Ag-bearing DCs were infrequent at high T cell precursor frequency, they were readily observed for a period of at least 2 days when lower numbers of T cells were used. We provide evidence that, when present in high numbers, Ag-specific T cells still gained access to the DC surface but were competing for the limited number of sites on DCs with sufficient peptide-MHC complexes for the establishment of a long-lived interaction. Consistent with these findings, we showed that restoration of peptide-MHC level on DCs at late time points was sufficient to recover interactions between activated T cells and DCs. Thus, the period during which CD4 T cells continue to establish stable interactions with DCs is longer than previously thought, and its duration is dictated by both Ag levels and T cell numbers, providing a feedback mechanism for the termination of CD4 T cell responses.
authors.affiliation: Institut Pasteur, G5 Dynamiques des Réponses Immunes, F-75015 Paris, France.
authors.forename: Zacarias
authors.initials: Z
authors.lastname: Garcia
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Pradelli
authors.forename: Susanna
authors.initials: S
authors.lastname: Celli
authors.forename: Hélène
authors.initials: H
authors.lastname: Beuneu
authors.forename: Aurélie
authors.initials: A
authors.lastname: Simon
authors.forename: Philippe
authors.initials: P
authors.lastname: Bousso
mesh_terms: D000818:Animals; D000941:Antigens / Q000737:chemistry*; D001667:Binding, Competitive; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002450:Cell Communication; D002469:Cell Separation; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000737:chemistry; D017785:Photons; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
chemical_list: D000941:Antigens; D010455:Peptides