The HLA-ER/HLA-ER genotype affects the natural course of hepatitis C virus (HCV) infection and is associated with HLA-E-Restricted recognition of an HCV-Derived peptide by interferon-γ-secreting human CD8+ T cells

Abstract

Recently, we showed chronic hepatitis C to be associated with increased expression of HLA-E and identified peptide hepatitis C virus (HCV) core amino acids 35-44 as a ligand for HLA-E that stabilizes HLA-E expression, favoring inhibition of natural killer cell cytotoxicity. Here we describe HLA-E-restricted recognition of peptide HCV core amino acids 35-44 by CD8 + T cells. Frequency of HLA-E-restricted responses was significantly higher in patients homozygous for the HLAER allele (60% vs 38%; Pp.038). Moreover, we found that the HLA-ER allelic variant confers protection against chronic infection with HCV genotypes 2 and 3. Taken together, our data indicate an important immunomodulating function of HLA-E in hepatitis C. © 2009 by the Infectious Diseases Society of America.