Differential presentation of endogenous and exogenous hepatitis B surface antigens influences priming of CD8(+) T cells in an epitope-specific manner

作者：Riedl Petra; Reiser Michael; Stifter Katja; Krieger Jana; Schirmbeck Reinhold^*

来源：European Journal of Immunology, 2014, 44(7): 1981-1991.

DOI：10.1002/eji.201343933

• CD8(+) T-cell-mediated immunodominance
• Endogenous and exogenous antigens
• Hepatitis B virus
• Transgenic mice
• Vaccination

Little is known about whether presentation of endogenous and exogenous hepatitis B virus (HBV) surface antigens on APCs targeted by vaccination and/or virus-harboring hepatocytes influences de novo priming of CD8(+) T cells. We showed that surface antigen-expressing transfectants exclusively display a K-b/S190 epitope, whereas cells pulsed with recombinant surface particles (rSPs) exclusively present a K-b/S208 epitope to CD8(+) T cells. The differential presentation of these epitopes largely reflects the selective, but not exclusive, priming of K-b/S190-and K-b/S208-specific T cells in C57BL/6 mice by endogenous/DNA-or exogenous/protein-based vaccines, respectively. Silencing the K-b/S190 epitope (K-b/S190(V194F)) in antigen-expressing vectors rescued the presentation of the K-b/S208 epitope in stable transfectants and significantly enhanced priming of K-b/S208-specific T cells in C57BL/6 mice. A K-b/S190-mediated immunodominance operating in surface antigen-expressing cells, but not in rSP-pulsed cells, led to an efficient suppression in the presentation of the K-b/S208 epitope and a consequent decrease in the priming of K-b/S208-specific T cells. This K-b/S190-mediated immunodominance also operated in 1.4HBV-S-mut transgenic (tg) hepatocytes selectively expressing endogenous surface antigens and allowed priming of K-b/S208-but not K-b/S190-specific T cells in 1.4HBV-S-mut tg mice. However, IFN-gamma(+) K-b/S208-specific T cells could not inhibit HBV replication in the liver of 1.4HBV-S-mut tg mice. These results have practical implications for the design of T-cell-stimulating therapeutic vaccines.

• 出版日期2014-7