The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20070489
The Journal of Experimental Medicine, Vol. 204, No. 9, 2187-2198
The Rockefeller University Press, 0022-1007 $30.00
© Kastenmuller et al.
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Article

 Cross-competition of CD8+ T cells shapes the immunodominance hierarchy during boost vaccination

Wolfgang Kastenmuller2,3,4, Georg Gasteiger1,2,3, Julian H. Gronau1, Robert Baier1,2,3, Ronny Ljapoci1, Dirk H. Busch2,3,5, and Ingo Drexler1,2,3

1 Institute of Molecular Virology, 2 Antigen-specific Immunotherapy Clinical Cooperation Group, and 3 Immune Monitoring Clinical Cooperation Group, National Research Center for Environment and Health, 81675 Munich, Germany
4 Institute of Virology, Technical University Munich, 81675 Munich, Germany
5 Institute for Medical Microbiology, Immunology and Hygiene, Technical University Munich, 81675 Munich, Germany

CORRESPONDENCE Ingo Drexler:drexler{at}gsf.de

CD8+ T cell responses directed against multiple pathogen-derived epitopes are characterized by defined immunodominance hierarchy patterns. A possible explanation for this phenomenon is that CD8+ T cells of different specificities compete for access to epitopes on antigen-presenting cells, and that the outcome of this so-called cross-competition reflects the number of induced T cells. In our study using a vaccinia virus infection model, we found that T cell cross-competition is highly relevant during boost vaccination, thereby shaping the immunodominance hierarchy in the recall. We demonstrate that competition was of no importance during priming and was unaffected by the applied route of immunization. It strongly depended on the timing of viral antigen expression in infected APCs, and it was characterized by poor proliferation of T cells recognizing epitopes derived from late viral proteins. To our knowledge, this is the first demonstration of the functional importance of T cell cross-competition during a viral infection. Our findings provide a basis for novel strategies for how boost vaccination to defined antigens can be selectively improved. They give important new insights into the design of more efficient poxviral vectors for immunotherapy.

Abbreviations used: CEF, chicken embryo fibroblast; CVA, chorioallantois VV Ankara; IU, infectious unit; LCMV, lymphocytic choriomeningitis virus; MOI, multiplicity of infection; MVA, modified VV Ankara; VV, vaccinia virus.

W. Kastenmuller and G. Gasteiger contributed equally to this paper.

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