Identification of HCMV-derived T cell epitopes in seropositive individuals through viral deletion models
| Autor: | Janet Kerstin Peper, Annika Nelde, Daniel J. Kowalewski, Hans-Georg Rammensee, Cosima Zimmermann, Maren Lübke, Liane Bauersfeld, Anne Halenius, Oliver Kohlbacher, Juliane S. Walz, Stefanie Spalt, Hartmut Hengel, Stefan Stevanovic, Leon Bichmann, Vu Thuy Khanh Le-Trilling, Ana Marcu |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Human cytomegalovirus viruses T cell Immunology Medizin Cytomegalovirus Epitopes T-Lymphocyte Human leukocyte antigen CD8-Positive T-Lymphocytes Biology Technical Advances and Resources Epitope Cell Line 03 medical and health sciences 0302 clinical medicine Antigen medicine Humans Immunology and Allergy Antigens Viral Research Articles virus diseases biochemical phenomena metabolism and nutrition medicine.disease Virology 030104 developmental biology medicine.anatomical_structure Cell culture Cytomegalovirus Infections Immunologic Memory Memory T cell CD8 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | This work demonstrates a novel strategy that enables the identification of HCMV-derived T cell epitopes by mass spectrometry. It provides a panel of novel T cell epitopes and presents evidence for their involvement in physiologic immune control of HCMV infections. In healthy individuals, immune control of persistent human cytomegalovirus (HCMV) infection is effectively mediated by virus-specific CD4+ and CD8+ T cells. However, identifying the repertoire of T cell specificities for HCMV is hampered by the immense protein coding capacity of this betaherpesvirus. Here, we present a novel approach that employs HCMV deletion mutant viruses lacking HLA class I immunoevasins and allows direct identification of naturally presented HCMV-derived HLA ligands by mass spectrometry. We identified 368 unique HCMV-derived HLA class I ligands representing an unexpectedly broad panel of 123 HCMV antigens. Functional characterization revealed memory T cell responses in seropositive individuals for a substantial proportion (28%) of these novel peptides. Multiple HCMV-directed specificities in the memory T cell pool of single individuals indicate that physiologic anti-HCMV T cell responses are directed against a broad range of antigens. Thus, the unbiased identification of naturally presented viral epitopes enabled a comprehensive and systematic assessment of the physiological repertoire of anti-HCMV T cell specificities in seropositive individuals. |
| Databáze: | OpenAIRE |
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