Cytotoxic T Cells

Little is known about the CTL response during acute or chronic HDV infection and its contribution to elimination of HDV in a subset of patients. Staining of stimulated peripheral blood mononuclear cells (PBMC) of patients with tetramer complexes loaded with peptides aa 26-34 and 43-51 showed significant binding (Fig. 2) (Huang et al. 2004). Interestingly, these patients presented with inactive disease (HDV RNA negative), whereas the patients with PBMCs without binding to these peptides had active disease (HDV RNA positive). For one patient the frequencies of peptide-specific CD8+ T cells increased significantly after peptide stimulation. ELISPOT assays also confirmed that these cells were functional to HDV. These two HLA-A*0201-restricted CD8+ T-cell epitopes (genotype 1) were identified in HLA-A*0201 transgenic mice that were immunized with plasmid DNA coding for the large HDAg. Splenocytes were screened directly ex vivo with tetramers presenting potential HLA-A*0201-restricted HDV peptides. Two of six tetramers loaded with epitopes aa 26-34 and 43-51, respectively, showed significantly enhanced responses in HLA-A*0201 transgenic mice after immunization. After stimulation in vitro, both CTL lines ofmice were able to trigger specific CTL responses to peptides 26-34 or 43-51.

0 0

Post a comment