T cell antigen discovery using soluble vaccinia proteome reveals recognition of antigens with both virion and non-virion association*
| Autor: | D. Huw Davies, Aarti Jain, Jo A. Tucker, Gary Hermanson, Xiaowu Liang, Rie Nakajima, Sookhee Chun, Philip L. Felgner, Jozelyn Pablo |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Proteome
viruses CD8-Positive T-Lymphocytes Inbred C57BL chemistry.chemical_compound Mice Receptors Immunology and Allergy 2.1 Biological and endogenous factors Viral Aetiology ORFeome Antigens Viral virus diseases Humoral Cell biology medicine.anatomical_structure Infectious Diseases Antigen Infection Biotechnology T cell Immunology Receptors Antigen T-Cell Vaccinia virus Biology Article Vaccine Related Interferon-gamma Immune system Rare Diseases Th2 Cells Biodefense medicine Animals Small Pox Antigens Prevention Immunity Th1 Cells T-Cell Virology Immunity Humoral Mice Inbred C57BL Emerging Infectious Diseases Membrane protein chemistry Immunization Vaccinia CD8 Spleen |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950), vol 193, iss 4 |
| Popis: | Vaccinia virus (VACV) is a useful model system for understanding the immune response to a complex pathogen. Proteome-wide Ab profiling studies reveal the humoral response to be strongly biased toward virion-associated Ags, and several membrane proteins induce Ab-mediated protection against VACV challenge in mice. Some studies have indicated that the CD4 response is also skewed toward proteins with virion association, whereas the CD8 response is more biased toward proteins with early expression. In this study, we have leveraged a VACV strain Western Reserve (VACV-WR) plasmid expression library, produced previously for proteome microarrays for Ab profiling, to make a solubilized full VACV-WR proteome for T cell Ag profiling. Splenocytes from VACV-WR–infected mice were assayed without prior expansion against the soluble proteome in assays for Th1 and Th2 signature cytokines. The response to infection was polarized toward a Th1 response, with the distribution of reactive T cell Ags comprising both early and late VACV proteins. Interestingly, the proportions of different functional subsets were similar to that present in the whole proteome. In contrast, the targets of Abs from the same mice were enriched for membrane and other virion components, as described previously. We conclude that a “nonbiasing” approach to T cell Ag discovery reveals a T cell Ag profile in VACV that is broader and less skewed to virion association than the Ab profile. The T cell Ag mapping method developed in the present study should be applicable to other organisms where expressible “ORFeome” libraries are also available, and it is readily scalable for larger pathogens. |
| Databáze: | OpenAIRE |
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