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01-08-2008 | Original Article

Sequence uniqueness and sequence variability as modulating factors of human anti-HCV humoral immune response

Authors: Darja Kanduc, Luciana Tessitore, Guglielmo Lucchese, Anthony Kusalik, Emanuel Farber, Francesco M. Marincola

Published in: Cancer Immunology, Immunotherapy | Issue 8/2008

Abstract

We recently compared the HCV polyprotein to the human proteome in order to test whether amino acid sequences unique to the virus could represent immunodominant epitopic determinants of the human humoral immune response against HCV. We identified a relatively limited number of HCV fragments with no/low similarity to the human host that represented exclusive HCV motifs. In this study, the peptides corresponding to low/zero similarity sequences were synthesized and assayed with HCV-infected sera. With different patterns, the synthetic HCV peptides corresponding to low/zero similarity sequences were found to be immunoreactive. In particular, the HCV E1 (315–323) HRMAWDMMM, HCV E2/NS1 (547–555) NWFGCTWMN, and HCV NS5 (2638–2646) YDTRCFDST sequences were immunodominant in the HCV-infected cohort under study. These three peptides correspond to sequences that are endowed with low-similarity to the human proteome, are highly conserved among various HCV strains, and have, potentially, a scarce susceptibility to proteolytic attacks. These data may be of help in defining the multiple factors which concur in the modulation of the human immune response against HCV, eventually providing information for the design of effective anti-HCV vaccines.

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Title: Sequence uniqueness and sequence variability as modulating factors of human anti-HCV humoral immune response
Authors: Darja Kanduc
Luciana Tessitore
Guglielmo Lucchese
Anthony Kusalik
Emanuel Farber
Francesco M. Marincola
Publication date: 01-08-2008
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 8/2008
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-008-0456-y

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