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.
Identification of HCMV-derived T cell epitopes in seropositive individuals through viral deletion models
- Views Icon Views
- Share Icon Share
- Tools Icon Tools
- Search Site
Maren Lübke, Stefanie Spalt, Daniel J. Kowalewski, Cosima Zimmermann, Liane Bauersfeld, Annika Nelde, Leon Bichmann, Ana Marcu, Janet Kerstin Peper, Oliver Kohlbacher, Juliane S. Walz, Vu Thuy Khanh Le-Trilling, Hartmut Hengel, Hans-Georg Rammensee, Stefan Stevanović, Anne Halenius; Identification of HCMV-derived T cell epitopes in seropositive individuals through viral deletion models. J Exp Med 2 March 2020; 217 (3): e20191164. doi: https://doi.org/10.1084/jem.20191164
Download citation file: