Induction of cytotoxic T lymphocyte activity by immunization with recombinant Semliki Forest virus: indications for cross-priming.
For the rational design of vaccines capable of inducing CD8+ T cell responses knowledge of the identity of the antigen-presenting cell (APC) and the mechanism of antigen presentation is very important. Here, we address these issues for alphavirus-based immunization, in particular immunization with recombinant Semliki Forest virus (rSFV). Studies with dendritic cells (DCs) from various origins revealed that rSFV has a very limited capacity to transfect this cell type in vitro. To further investigate in vivo whether rSFV transfects professional antigen-presenting cells directly or whether the antigens reach APCs via a mechanism of cross-priming we compared the immunological effects of three different SFV-constructs encoding the influenza nucleoprotein (NP). These constructs differ in the amount of NP produced per cell or in the stability of the NP, respectively. Induction of cytotoxic T lymphocytes (CTLs) appeared to benefit from a large amount of stable antigen. In contrast, rapid antigen degradation, and thus availability of antigenic peptides in the transfected cell, was found to be disadvantageous. Based on these in vitro and in vivo results, we hypothesize that antigen presentation after SFV-based immunization proceeds via a mechanism in which APCs are not transfected directly but acquire antigen from other transfected cells and present it to CTLs in a process of cross-priming.
Department of Medical Microbiology, Molecular Virology Section, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands. a.l.w.huckriede@med.rug.nl
Anke
A
Huckriede
Laura
L
Bungener
Marijke
M
Holtrop
Jacqueline
J
de Vries
Barry-Lee
BL
Waarts
Toos
T
Daemen
Jan
J
Wilschut
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002460:Cell Line; D002860:Chromium Radioisotopes; D003001:Cloning, Molecular; D006224:Cricetinae; D003429:Cross Reactions; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D005805:Genes, MHC Class I / Q000276:immunology; D006801:Humans; D051379:Mice; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology; D010957:Plasmids / Q000235:genetics; D012672:Semliki forest virus / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D025801:Ubiquitin / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D002860:Chromium Radioisotopes; D009698:Nucleoproteins; D025801:Ubiquitin; D014614:Vaccines, Synthetic; D014765:Viral Vaccines