Published in

American Society for Microbiology, Journal of Virology, 10(85), p. 5232-5236, 2011

DOI: 10.1128/jvi.00093-11

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Immunodominance of HLA-A2-Restricted Hepatitis C Virus-Specific CD8+ T Cell Responses Is Linked to Naive-Precursor Frequency

Journal article published in 2011 by Julia Schmidt, Christoph Neumann-Haefelin, Tayibe Altay, Emma Gostick, David A. Price, Volker Lohmann ORCID, Hubert E. Blum, Robert Thimme
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

ABSTRACT The impact of naïve-precursor frequency on human virus-specific CD8 + T cell immunodominance is not well understood. Using a recently developed major histocompatibility complex (MHC) class I tetramer enrichment protocol, we found a conserved hierarchy and a >10-fold difference in naïve-precursor frequencies across three HLA-A2-restricted hepatitis C virus (HCV)-specific epitopes. Importantly, the NS3 1406 epitope with the highest naïve-precursor frequency in healthy donors was also the most frequently targeted epitope in a large cohort of chronically HCV-infected patients, both ex vivo and after in vitro stimulation. These results indicate for the first time that immunodominance in a human viral infection is linked to naïve-precursor frequency.