The HLA-E(R)/HLA-E(R) 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-gamma-Secreting Human CD8(+) T Cells.

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 HLA-E(R) allele (60% vs 38%; [Formula: see text]). Moreover, we found that the HLA-E(R) 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. [ABSTRACT FROM AUTHOR]