title: In vivo imaging of T cell priming.
abstract: The rules by which naïve T cells decide whether and how to respond to antigenic stimuli are incompletely understood. Using multiphoton intravital microscopy (MP-IVM) in lymph nodes (LNs), we have shown that CD8+ T cells are primed by antigen-presenting dendritic cells (DCs) in three consecutive phases. During phase one, T cells undergo brief serial contacts with many DCs for several hours after homing into the LNs. Subsequently, during phase two, T cells engage in prolonged stable interactions with DCs. Finally, in the third phase, T cells return to transient interactions with DCs as they begin to proliferate and eventually leave the LNs. We have examined the influence of antigen dose on the duration of phase one by systematically varying both the number of cognate peptide-major histocompatability (pMHC) complexes per DC and the density of cognate pMHC complex-presenting DCs per LN. The duration of phase one and the kinetics of CD8+ T cell activation were inversely correlated with both parameters. Very few pMHC complexes were needed for full T cell activation and effector differentiation. Furthermore, there was a sharp threshold of antigen dose below which T cells did not transition to phase two but continued to migrate until they exited the LN, unactivated. The stability of peptide binding to MHC was a critical determinant of this threshold antigen dose in vivo. Our results suggest an integrative mechanism that allows T cells to reach an informed decision about whether to respond, based on the overall antigen dose encountered.
authors: Department of Pathology and the Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA.
authors: Sarah E
authors: SE
authors: Henrickson
authors: Thorsten R
authors: TR
authors: Mempel
authors: Irina B
authors: IB
authors: Mazo
authors: Bai
authors: B
authors: Liu
authors: Maxim N
authors: MN
authors: Artyomov
authors: Huan
authors: H
authors: Zheng
authors: Antonio
authors: A
authors: Peixoto
authors: Michael
authors: M
authors: Flynn
authors: Balimkiz
authors: B
authors: Senman
authors: Tobias
authors: T
authors: Junt
authors: Hing C
authors: HC
authors: Wong
authors: Arup K
authors: AK
authors: Chakraborty
authors: Ulrich H
authors: UH
authors: von Andrian
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D006649:Histocompatibility Antigens / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D036641:Microscopy, Fluorescence, Multiphoton; D010455:Peptides / Q000276:immunology; D013997:Time Factors
chemical_list: D006649:Histocompatibility Antigens; D010455:Peptides