Key result
AAV-2 and AAV-8 capsids share a conserved CD8+ T cell epitope recognized in murine models.
Why the study?
The impact of AAV capsid-specific CD8+ T cells on AAV-mediated gene transfer was not fully understood, necessitating identification of CD8+ T cell epitopes for AAV capsids.
Identification of AAV capsid-specific CD8+ T cell epitopes in mice will facilitate studies of immune responses to AAV vectors in gene transfer.
Does not guide clinical AAV vector choice; extends murine models for studying capsid-specific T-cell responses in gene therapy.
Adeno-associated virus has been developed for use as a gene transfer vector. To understand the impact of AAV capsid-specific CD8(+) T cells on AAV-mediated gene transfer, we identified CD8(+) T cell epitopes for AAV-2 and AAV-8 capsid in C57BL/6 (H-2(b) MHC haplotype) and BALB/c (H-2(d) MHC haplotype) mice. Mice of both the H-2(b) and the H-2(d) haplotypes recognized epitopes on AAV-2 and AAV-8 capsid. T cells from H-2(b) mice recognized an epitope that was conserved between AAV-2 and AAV-8 capsid. Cross-reactivity of AAV-specific CD8(+) T cells induced by different AAV serotypes may have important implications for gene transfer. Identification of these epitopes will facilitate studies of immune response to AAV capsid in mouse models.
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Sabatino et al. (2005) studied this question. AAV-2 and AAV-8 capsid was evaluated on Identification of CD8+ T cell epitopes. Mice of both H-2b and H-2d haplotypes recognized epitopes on AAV-2 and AAV-8 capsids, with H-2b mice recognizing a conserved epitope between the two serotypes.
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