title: Cross-competition of CD8+ T cells shapes the immunodominance hierarchy during boost vaccination.
abstract: 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.
authors: Institute of Molecular Virology, Antigen-specific Immunotherapy Clinical Cooperation Group, National Research Center for Environment and Health, 81675 Munich, Germany.
authors: Wolfgang
authors: W
authors: Kastenmuller
authors: Georg
authors: G
authors: Gasteiger
authors: Julian H
authors: JH
authors: Gronau
authors: Robert
authors: R
authors: Baier
authors: Ronny
authors: R
authors: Ljapoci
authors: Dirk H
authors: DH
authors: Busch
authors: Ingo
authors: I
authors: Drexler
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D002642:Chick Embryo; D045142:Cross-Priming / Q000276:immunology*; D005260:Female; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D007117:Immunization, Secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors; D014611:Vaccination; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D014764:Viral Proteins
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