An Extremely Diverse CD4 Response to Vaccinia Virus in Humans Is Revealed by Proteome-Wide T-Cell Profiling
- 15 July 2008
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 82 (14), 7120-7134
- https://doi.org/10.1128/jvi.00453-08
Abstract
CD4 T cells are required for the maintenance and recall of antiviral CD8 T cells and for antibody responses. Little is known concerning the overall architecture of the CD4 response to complex microbial pathogens. In a whole-proteome approach, 180 predicted open reading frames (ORFs) in the vaccinia virus genome were expressed and tested using responder cells from 20 blood samples from 11 vaccinees. Validation assays established the sensitivity and specificity of the system. Overall, CD4 responses were detected for 122 ORFs (68%). A mean of 39 ORFs were recognized per person (range, 13 to 63). The most frequently recognized ORFS were present in virions, including A3L and A10L (core proteins), WR148 (a fragmented homolog of an orthopoxvirus protein that forms inclusions in cells), H3L (a membrane protein), D13L (a membrane scaffold protein), and L4R (a nucleic acid binding protein). Serum immunoglobulin G profiling by proteome microarray detected responses to 45 (25%) of the ORFs and confirmed recent studies showing a diverse response directed to membrane and nonmembrane antigens. Our results provide the first empirical whole-proteome data set regarding the global CD4 response to full-length proteins in a complex virus and are consistent with the theory that abundant structural proteins are immunodominant.Keywords
This publication has 77 references indexed in Scilit:
- Antibody Profiling by Proteome Microarray Reveals the Immunogenicity of the Attenuated Smallpox Vaccine Modified Vaccinia Virus Ankara Is Comparable to That of DryvaxJournal of Virology, 2008
- Human CD4+ T Cell Epitopes from Vaccinia Virus Induced by Vaccination or InfectionPLoS Pathogens, 2007
- Th1 and Th2 Cells Help CD8 T-Cell ResponsesInfection and Immunity, 2007
- CD127+CCR5+CD38+++CD4+Th1 Effector Cells Are an Early Component of the Primary Immune Response to Vaccinia Virus and Precede Development of Interleukin-2+Memory CD4+T CellsJournal of Virology, 2006
- Human T-Cell Responses to Vaccinia Virus Envelope ProteinsJournal of Virology, 2006
- Identification of Vaccinia CD8+ T-Cell Epitopes Conserved among Vaccinia and Variola Viruses Restricted by Common MHC Class I Molecules, HLA-A2 or HLA-B7Human Immunology, 2006
- A consensus epitope prediction approach identifies the breadth of murine TCD8+-cell responses to vaccinia virusNature Biotechnology, 2006
- Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjectsThe Journal of Experimental Medicine, 2005
- The complete genome sequence of Francisella tularensis, the causative agent of tularemiaNature Genetics, 2005
- Genome sequence of the human malaria parasite Plasmodium falciparumNature, 2002