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J Immunol. 2014 Aug 15;193(4):1567-77. doi: 10.4049/jimmunol.1400667. Epub 2014 Jul 7.

Clonotypic composition of the CD4+ T cell response to a vectored retroviral antigen is determined by its speed.

Author information

1
Division of Immunoregulation, Medical Research Council National Institute for Medical Research, London NW7 1AA, United Kingdom;
2
Institute for Virology, University Hospital Essen, University Duisburg-Essen, Essen 45147, Germany;
3
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840;
4
Department of Immunology, University of Washington, Seattle, WA 98195; and.
5
Division of Immunoregulation, Medical Research Council National Institute for Medical Research, London NW7 1AA, United Kingdom; Department of Medicine, Faculty of Medicine, Imperial College London, London W2 1PG, United Kingdom gkassio@nimr.mrc.ac.uk.

Abstract

The mechanisms whereby different vaccines may expand distinct Ag-specific T cell clonotypes or induce disparate degrees of protection are incompletely understood. We found that several delivery modes of a model retroviral Ag, including natural infection, preferentially expanded initially rare high-avidity CD4(+) T cell clonotypes, known to mediate protection. In contrast, the same Ag vectored by human adenovirus serotype 5 induced clonotypic expansion irrespective of avidity, eliciting a predominantly low-avidity response. Nonselective clonotypic expansion was caused by relatively weak adenovirus serotype 5-vectored Ag presentation and was reproduced by replication-attenuated retroviral vaccines. Mechanistically, the potency of Ag presentation determined the speed and, consequently, completion of the CD4(+) T cell response. Whereas faster completion retained the initial advantage of high-avidity clonotypes, slower completion permitted uninhibited accumulation of low-avidity clonotypes. These results highlighted the importance of Ag presentation patterns in determining the clonotypic composition of vaccine-induced T cell responses and ultimately the efficacy of vaccination.

PMID:
25000983
PMCID:
PMC4119786
DOI:
10.4049/jimmunol.1400667
[Indexed for MEDLINE]
Free PMC Article
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