Degree of cross-genotype reactivity of hepatitis C virus-specific CD8+ T cells directed against NS3.
The inherent sequence diversity of the hepatitis C virus (HCV) with the existence of multiple genotypes that differ up to 20% at the amino acid level represents one of the major obstacles for immune control. Accordingly, immune control of a heterologous virus challenge, particularly across genotypes, is difficult to achieve; however, the overall role of genotype-specific sequence differences has not yet been defined at the epitope level. The aim of this study was to determine the role of genotype-specific sequence differences for the CD8+ T cell response against HCV. We analyzed a cohort of anti-HCV-positive injection drug users infected with HCV genotype 1 (n = 17) or genotype 3 (n = 22) or undetectable HCV-RNA (n = 14) with overlapping peptides covering consensus sequences of NS3 from both genotypes. Importantly, the majority of HCV-specific CD8 T cells were specific for one genotype only indicating that sequence differences between genotypes are relevant at the epitope level. Interestingly, T cells active against both genotypes were significantly more frequent in HCV-RNA-negative subjects. Of note, we identified five subjects with undetectable viremia and coexistence of two T cell populations-one for each genotype-suggesting immune control of two different genotypes.


CONCLUSIONS
We systematically analyzed the degree of cross-genotype reactivity of HCV-specific T cells and have shown that CD8 responses targeting different HCV genotypes can be primed in the same individual and that such responses potentially characterize a subgroup among injection drug users being protected from chronic HCV infection.
Giugliano
Silvia
S
Department of Virology, University of Essen, Essen, Germany.
Oezkan
Filiz
F
Bedrejowski
Mathias
M
Kudla
Markus
M
Reiser
Markus
M
Viazov
Sergei
S
Scherbaum
Norbert
N
Roggendorf
Michael
M
Timm
Joerg
J
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D055030:Drug Users; D000939:Epitopes; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000939:Epitopes; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases