Determination of specific CD4 and CD8 T cell epitopes after AAV2- and AAV8-hF.IX gene therapy

Academic Article


  • The application of AAV2 or AAV8 vectors for delivery of human coagulation factor IX (hF.IX) is a promising gene therapy for hemophilia B. One major limitation of this therapy is the development of antibodies and a cytotoxic T lymphocyte (CTL) response against both the vector capsid and the transgene. We determined the class I and class II MHC peptide epitopes for AAV2, AAV8, and hF.IX after administration of AAV-2-hF.IX or AAV8-hF.IX in H2b (C57BL/6), H2d (BALB/c), or H2k (C3H) strains of mice. The results indicate that the AAV2 capsid peptide AA373-381, the AAV8 capsid peptide AA50-58, and the hF.IX transgene peptide AA311-319 can elicit a CTL response as indicated by an IFN-γ ELISPOT assay and an in vivo CTL assay. Furthermore, a strong H2k MHC II-restricted Th1 response can be elicited in C3H mice by the AAV8 capsid peptide AA126-140 and the hF.IX peptide AA108-122, whereas a strong Th2 response can be elicited by the AAV2 peptide AA475-489. These results show that specific CTL responses are generated to both AAV capsid epitopes and hF.IX epitopes after injection of AAV-hF.IX, and MHC class II epitopes derived from AAV-hF.IX promote development of either Th1 or Th2 cells. Copyright © The American Society of the Gene Therapy.
  • Published In

  • Molecular Therapy  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 23431076
  • Author List

  • Chen J; Wu Q; Yang PA; Hsu HC; Mountz JD
  • Start Page

  • 260
  • End Page

  • 269
  • Volume

  • 13
  • Issue

  • 2