Effect of HLA class II genotype on T helper lymphocyte responses and viralcontrol in hepatitis C virus infection

Hepatitis C virus (HCV) infection is very common worldwide, but has a broad range of outcomes. A minority of patients are able to clear infection spon taneously, and this is thought to be due to the emergence and maintenance o f effective cell-mediated immunity, particularly CD4+ T lymphocyte response s. Furthermore, genetic studies have indicated that HLA class II genotype s trongly influences the outcome of infection. We have therefore investigated the influence of the protective HLA class II haplotype (DQB1*0301, which i s in tight linkage disequilibrium with DRB1*1101) on the CD4+ T lymphocyte responses to HCV. We observe a strong association between this genotype and maintenance of a multispecific CD4+ T helper response. The effect on T hel per responses was also maintained after combination interferon-alpha /ribav irin therapy, although the latter influenced the pattern of viral antigens to which patients responded. This is the first disease in which an associat ion of HLA genotype with clinical outcome has been linked to an alteration of the immunological phenotype. The selection of protective peptides in tho se with the favourable HLA class II genotype may point in the direction of suitable vaccine candidates.