CD8+ T-cell responses to hepatitis C virus (HCV) are important in generating a successful immune response and spontaneously clearing
infection.
Human leukocyte antigen (HLA) class I presents viral
peptides to CD8+ T cells to permit detection of infected cells, and
tapasin is an important component of the
peptide loading complex for HLA class I. We sought to determine if
tapasin polymorphisms affected the outcome of HCV
infection. Patients with resolved or chronic HCV
infection were genotyped for the known G/C coding polymorphism in exon 4 of the
tapasin gene. In a European, but not a US, Caucasian population, the
tapasin G allele was significantly associated with the outcome of HCV
infection, being found in 82.5% of resolvers versus 71.3% of persistently infected individuals (P = 0.02, odds ratio [OR] = 1.90 95% confidence interval [CI] = 1.11-3.23). This was more marked at the
HLA-B locus at which heterozygosity of both
tapasin and
HLA-B was protective (P < 0.03). Individuals with an
HLA-B allele with an
aspartate at residue 114 and the
tapasin G allele were more likely to spontaneously resolve HCV
infection (P < 0.00003, OR = 3.2 95% CI = 1.6-6.6). Additionally, individuals with chronic HCV and the combination of an
HLA-B allele with an
aspartate at residue 114 and the
tapasin G allele also had stronger CD8+ T-cell responses (P = 0.02, OR = 2.58, 95% CI-1.05-6.5).
CONCLUSION:
Tapasin alleles contribute to the outcome of HCV
infection by synergizing with polymorphisms at
HLA-B in a population-specific manner. This polymorphism may be relevant for
peptide vaccination strategies against HCV
infection.