Antigen presentation kinetics control T cell/dendritic cell interactions and follicular helper T cell generation in vivo

Benson, R. A., Macleod, M. K.L. , Hale, B. G.H. , Patakas, A., Garside, P. and Brewer, J. M. (2015) Antigen presentation kinetics control T cell/dendritic cell interactions and follicular helper T cell generation in vivo. eLife, 4, e06994. (doi:10.7554/eLife.06994) (PMID:26258879) (PMCID:PMC4558563)

Benson, R. A., Macleod, M. K.L. , Hale, B. G.H. , Patakas, A., Garside, P. and Brewer, J. M. (2015) Antigen presentation kinetics control T cell/dendritic cell interactions and follicular helper T cell generation in vivo. eLife, 4, e06994. (doi:10.7554/eLife.06994) (PMID:26258879) (PMCID:PMC4558563)

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Abstract

The production of high affinity, class switched antibodies produced by B cells hinges on the effective differentiation of T follicular helper (Tfh) cells. Here we define conditions specifically enhancing Tfh differentiation and providing protection in a model of influenza infection. Tfh responses were associated with prolonged antigen presentation by dendritic cells (DCs), which maintained T cell/DC interactions into stage 3 (>72 hr) of activation. Blocking stage 3 interactions ablated Tfh generation, demonstrating a causal link between T cell-DC behaviour and functional outcomes. The current data therefore explain how duration of antigen presentation affects the dynamics of T cell-DC interactions and consequently determine Tfh cell differentiation in the developing immune response.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Brewer, Professor James and Garside, Professor Paul and Hale, Dr Benjamin and Macleod, Dr Megan and Patakas, Dr Agapitos and Benson, Dr Robert
Authors: Benson, R. A., Macleod, M. K.L., Hale, B. G.H., Patakas, A., Garside, P., and Brewer, J. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:eLife
Publisher:eLife Sciences Publications
ISSN:2045-5267
ISSN (Online):2050-084X
Copyright Holders:Copyright © 2015 Benson et al.
First Published:First published in eLife 4:e06994
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
604512UBIFLU: Ubiquitin Signalling Pathways Required for Influenza Virus Replication: Biological Characterisation and Identification of Novel Drug TargetsBenjamin HaleWellcome Trust (WELLCOME)100034/Z/12/ZMVLS III - CENTRE FOR VIRUS RESEARCH
524791Investigating the contributions of antigen targeting and inflammation to adjuvant functionJames BrewerWellcome Trust (WELLCOME)085589/B/08/ZIII -IMMUNOLOGY