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© Michaela Muller-Trutwin
HIV
Publication : Journal of immunology (Baltimore, Md. : 1950)

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of immunology (Baltimore, Md. : 1950) - 07 Jul 2014

Thorborn G, Ploquin MJ, Eksmond U, Pike R, Bayer W, Dittmer U, Hasenkrug KJ, Pepper M, Kassiotis G

Link to Pubmed [PMID] – 25000983

J. Immunol. 2014 Aug;193(4):1567-77

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.

http://www.ncbi.nlm.nih.gov/pubmed/25000983