Details

Autor(en) / Beteiligte

• Riedl, Petra
• Reiser, Michael
• Stifter, Katja
• Krieger, Jana
• Schirmbeck, Reinhold

Titel

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

Ist Teil von

• European journal of immunology, 2014-07, Vol.44 (7), p.1981-1991

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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 Kb/S190 epitope, whereas cells pulsed with recombinant surface particles (rSPs) exclusively present a Kb/S208 epitope to CD8+ T cells. The differential presentation of these epitopes largely reflects the selective, but not exclusive, priming of Kb/S190‐ and Kb/S208‐specific T cells in C57BL/6 mice by endogenous/DNA‐ or exogenous/protein‐based vaccines, respectively. Silencing the Kb/S190 epitope (Kb/S190V194F) in antigen‐expressing vectors rescued the presentation of the Kb/S208 epitope in stable transfectants and significantly enhanced priming of Kb/S208‐specific T cells in C57BL/6 mice. A Kb/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 Kb/S208 epitope and a consequent decrease in the priming of Kb/S208‐specific T cells. This Kb/S190‐mediated immunodominance also operated in 1.4HBV‐Smut transgenic (tg) hepatocytes selectively expressing endogenous surface antigens and allowed priming of Kb/S208‐ but not Kb/S190‐specific T cells in 1.4HBV‐Smut tg mice. However, IFN‐γ+ Kb/S208‐specific T cells could not inhibit HBV replication in the liver of 1.4HBV‐Smut tg mice. These results have practical implications for the design of T‐cell‐stimulating therapeutic vaccines.