Role of MHC Haplotype in HCV Persistence

It is unlikely that the outcome of the immune response is entirely genetically determined. For CD4+ T cells, it is possible that the MHC class II haplotype and thus the range and type of epitopes that are targeted during the immune response play some role in HCV persistence. Some MHC class II allotypes, such as HLA-DRß 1*0701, have been associated with HCV persistence (Fanning et al., 2001), while other allotypes (DRß 1*0101, HLA-DRß1*1101, and DQß 1*0301) are linked to sustained T helper response and/or a self-limited disease (Alric et al., 1997; Minton et al., 1998; Thursz et al., 1999; Harcourt et al., 2001). Likewise, the CD8+ T cell response during acute hepatitis does not seem to be preferentially biased toward any particular HCV protein or epitope. Some MHC class I allotypes, such as HLA-Cw*04, have been associated with HCV persistence (Thio et al., 2002) and HLA-B27 with protection (Neumann-Haefelin et al., 2006). However, some studies (Cooper et al., 1999; Lauer et al., 2002; Mizukoshi et al., 2002) have failed to identify any association between CTL specificity and the different MHC class I epitopes predicted by algorithms for binding to some common HLA molecules, such as HLA-A2.1 (Battegay et al., 1995; Cerny et al., 1995; Erickson et al., 2001).

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