GM-CSF Production Allows the Identification of Immunoprevalent Antigens Recognized by Human CD4+ T Cells Following Smallpox Vaccination
| Autor: | Kingyee Law, Valeria Judkowski, Jon R. Appel, Mark K. Slifka, Atima Sharma, Marc A. Giulianotti, Feng Ge, Daniel C. Douek, Claudia Raja Gabaglia, Barney S. Graham, Patricia Norori, Radleigh G. Santos, Alcinette Bunying, Clemencia Pinilla |
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| Rok vydání: | 2011 |
| Předmět: |
CD4-Positive T-Lymphocytes
Viral Diseases Anatomy and Physiology viruses lcsh:Medicine Antigen Processing and Recognition CD8-Positive T-Lymphocytes chemistry.chemical_compound 0302 clinical medicine Immune Physiology Vaccinia Cytotoxic T cell lcsh:Science Smallpox vaccine Immune Response Antigens Viral Cells Cultured 0303 health sciences Multidisciplinary biology T Cells Vaccination 3. Good health Infectious Diseases medicine.anatomical_structure Cytokines Medicine Antibody Smallpox Vaccine Research Article Immune Cells T cell Immunology Antigen-Presenting Cells Vaccinia virus Cell Line Interferon-gamma 03 medical and health sciences Antigen medicine Humans Amino Acid Sequence Antigens Antigen-presenting cell Biology 030304 developmental biology Tumor Necrosis Factor-alpha lcsh:R Granulocyte-Macrophage Colony-Stimulating Factor HLA-DR Antigens Molecular Development Virology chemistry Immune System biology.protein Clinical Immunology lcsh:Q CD8 Developmental Biology Smallpox 030215 immunology |
| Zdroj: | PLoS ONE, Vol 6, Iss 9, p e24091 (2011) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | The threat of bioterrorism with smallpox and the broad use of vaccinia vectors for other vaccines have led to the resurgence in the study of vaccinia immunological memory. The importance of the role of CD4+ T cells in the control of vaccinia infection is well known. However, more CD8+ than CD4+ T cell epitopes recognized by human subjects immunized with vaccinia virus have been reported. This could be, in part, due to the fact that most of the studies that have identified human CD4+ specific protein-derived fragments or peptides have used IFN-γ production to evaluate vaccinia specific T cell responses. Based on these findings, we reasoned that analyzing a large panel of cytokines would permit us to generate a more complete analysis of the CD4 T cell responses. The results presented provide clear evidence that TNF-α is an excellent readout of vaccinia specificity and that other cytokines such as GM-CSF can be used to evaluate the reactivity of CD4+ T cells in response to vaccinia antigens. Furthermore, using these cytokines as readout of vaccinia specificity, we present the identification of novel peptides from immunoprevalent vaccinia proteins recognized by CD4+ T cells derived from smallpox vaccinated human subjects. In conclusion, we describe a "T cell-driven" methodology that can be implemented to determine the specificity of the T cell response upon vaccination or infection. Together, the single pathogen in vitro stimulation, the selection of CD4+ T cells specific to the pathogen by limiting dilution, the evaluation of pathogen specificity by detecting multiple cytokines, and the screening of the clones with synthetic combinatorial libraries, constitutes a novel and valuable approach for the elucidation of human CD4+ T cell specificity in response to large pathogens. |
| Databáze: | OpenAIRE |
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