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)

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: Patakas, Dr Agapitos and Hale, Dr Benjamin and Benson, Dr Robert and Brewer, Professor James and Garside, Professor Paul and Macleod, Dr Megan
• 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 > School of Infection & Immunity
• Journal Name: eLife
• Publisher: eLife Sciences Publications
• ISSN: 2050-084X
• 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
60451	2	UBIFLU: Ubiquitin Signalling Pathways Required for Influenza Virus Replication: Biological Characterisation and Identification of Novel Drug Targets	Benjamin Hale	Wellcome Trust (WELLCOME)	100034/Z/12/Z	MVLS III - CENTRE FOR VIRUS RESEARCH
52479	1	Investigating the contributions of antigen targeting and inflammation to adjuvant function	James Brewer	Wellcome Trust (WELLCOME)	085589/B/08/Z	III -IMMUNOLOGY