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Overcoming Original Antigenic Sin to Generate New CD8 T Cell IFN- Responses in an Antigen-Experienced Host¹

Centre for Immunology and Cancer Research, Princess Alexandra Hospital, University of Queensland, Woolloongabba, Brisbane, Australia

The failure to mount effective immunity to virus variants in a previously virus-infected host is known as original antigenic sin. We have previously shown that prior immunity to a virus capsid protein inhibits induction by immunization of an IFN- CD8⁺ T cell response to an epitope linked to the capsid protein. We now demonstrate that capsid protein-primed CD4⁺ T cells secrete IL-10 in response to capsid protein presented by dendritic cells, and deviate CD8⁺ T cells responding to a linked MHC class I-restricted epitope to reduce IFN- production. Neutralizing IL-10 while delivering further linked epitope, either in vitro or in vivo, restores induction by immunization of an Ag-specific IFN- response to the epitope. This finding demonstrates a strategy for overcoming inhibition of MHC class I epitopes upon immunization of a host already primed to Ag, which may facilitate immunotherapy for chronic viral infection or cancer.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Health and Medical Research Council Program Grant 351439 and Queensland Cancer Fund Project Grant 2004000983.

² Address correspondence and reprint requests to Dr. Xiao Song Liu, Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia. E-mail address: xliu{at}cicr.uq.edu.au

³ Abbreviations used in this paper: PV, papillomavirus; VLP, virus-like particle; cVLP, chimeric VLP; DC, dendritic cell; HPV, human PV; alum, aluminum hydroxide gel.