Murine CD8 T-cell functional avidity is stable in vivo but not in vitro: Independence from homologous prime/boost time interval and antigen density.


Journal

European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201

Informations de publication

Date de publication:
04 2020
Historique:
received: 15 08 2019
revised: 17 10 2019
accepted: 27 11 2019
pubmed: 1 12 2019
medline: 11 8 2020
entrez: 1 12 2019
Statut: ppublish

Résumé

It is known that for achieving high affinity antibody responses, vaccines must be optimized for antigen dose/density, and the prime/boost interval should be at least 4 weeks. Similar knowledge is lacking for generating high avidity T-cell responses. The functional avidity (FA) of T cells, describing responsiveness to peptide, is associated with the quality of effector function and the protective capacity in vivo. Despite its importance, the FA is rarely determined in T-cell vaccination studies. We addressed the question whether different time intervals for short-term homologous vaccinations impact the FA of CD8 T-cell responses. Four-week instead of 2-week intervals between priming and boosting with potent subunit vaccines in C57BL/6 mice did not improve FA. Equally, similar FA was observed after vaccination with virus-like particles displaying low versus high antigen densities. Interestingly, FA was stable in vivo but not in vitro, depending on the antigen dose and the time interval since T-cell activation, as observed in murine monoclonal T cells. Our findings suggest dynamic in vivo modulation for equal FA. We conclude that low antigen density vaccines or a minimal 4-week prime/boost interval are not crucial for the T-cell's FA, in contrast to antibody responses.

Identifiants

pubmed: 31785153
doi: 10.1002/eji.201948355
pmc: PMC7187562
doi:

Substances chimiques

Antigens 0
Peptides 0
Receptors, Antigen, T-Cell 0
Vaccines, Subunit 0
Vaccines, Virus-Like Particle 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

505-514

Subventions

Organisme : Swiss Cancer Research
ID : 3971-08-2016
Pays : International
Organisme : Swiss Cancer Research
ID : 4291-08-2017
Pays : International
Organisme : Ludwig Institute for Cancer Research
Pays : International
Organisme : NIBIB NIH HHS
ID : R01 EB022433
Pays : United States
Organisme : Alfred and Annemarie von Sick
Pays : International
Organisme : The Swiss National Science Foundation
ID : 310030-179459
Pays : International
Organisme : Cancer Research Institute
Pays : United States
Organisme : Université de Lausanne
Pays : International

Informations de copyright

© 2019 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Auteurs

Connie B Gilfillan (CB)

Department of Oncology, University of Lausanne, Switzerland.

Chensu Wang (C)

Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.

Mona O Mohsen (MO)

Inselspital, Universitaetsklinik RIA, Immunologie, Bern, Switzerland.
Jenner Institute, University of Oxford, Oxford, UK.

Nathalie Rufer (N)

Department of Oncology, University of Lausanne, Switzerland.
Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland.

Michael Hebeisen (M)

Department of Oncology, University of Lausanne, Switzerland.

Mathilde Allard (M)

Department of Oncology, University of Lausanne, Switzerland.

Grégory Verdeil (G)

Department of Oncology, University of Lausanne, Switzerland.

Darrell J Irvine (DJ)

Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.

Martin F Bachmann (MF)

Inselspital, Universitaetsklinik RIA, Immunologie, Bern, Switzerland.
Jenner Institute, University of Oxford, Oxford, UK.

Daniel E Speiser (DE)

Department of Oncology, University of Lausanne, Switzerland.
Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland.

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