Competition for antigen determines the stability of T cell-dendritic cell interactions during clonal expansion.
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.
Garcia
Zacarias
Z
Institut Pasteur, G5 Dynamiques des Réponses Immunes, F-75015 Paris, France.
Pradelli
Emmanuelle
E
Celli
Susanna
S
Beuneu
Hélène
H
Simon
Aurélie
A
Bousso
Philippe
P
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
D000941:Antigens; D010455:Peptides