PuSH - Publication Server of Helmholtz Zentrum München

Martin, L.K. ; Hollaus, A. ; Stahuber, A. ; Hübener, C. ; Fraccaroli, A. ; Tischer, J. ; Schub, A. ; Moosmann, A.

Cross-sectional analysis of CD8 T cell immunity to human herpesvirus 6B.

PLoS Pathog. 14:e1006991 (2018)
Publ. Version/Full Text Postprint Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Human herpesvirus 6 (HHV-6) is prevalent in healthy persons, causes disease in immunosuppressed carriers, and may be involved in autoimmune disease. Cytotoxic CD8 T cells are probably important for effective control of infection. However, the HHV-6-specific CD8 T cell repertoire is largely uncharacterized. Therefore, we undertook a virus-wide analysis of CD8 T cell responses to HHV-6. We used a simple anchor motif-based algorithm (SAMBA) to identify 299 epitope candidates potentially presented by the HLA class I molecule B*08:01. Candidates were found in 77 of 98 unique HHV-6B proteins. From peptide-expanded T cell lines, we obtained CD8 T cell clones against 20 candidates. We tested whether T cell clones recognized HHV-6-infected cells. This was the case for 16 epitopes derived from 12 proteins from all phases of the viral replication cycle. Epitopes were enriched in certain amino acids flanking the peptide. Ex vivo analysis of eight healthy donors with HLA-peptide multimers showed that the strongest responses were directed against an epitope from IE-2, with a median frequency of 0.09% of CD8 T cells. Reconstitution of T cells specific for this and other HHV-6 epitopes was also observed after allogeneic hematopoietic stem cell transplantation. We conclude that HHV-6 induces CD8 T cell responses against multiple antigens of diverse functional classes. Most antigens against which CD8 T cells can be raised are presented by infected cells. Ex vivo multimer staining can directly identify HHV-6-specific T cells. These results will advance development of immune monitoring, adoptive T cell therapy, and vaccines.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Randomized Controlled-trial; Chronic Tic Disorders; Parkinsons-disease; Health-care; Tourette-syndrome; Behavior-therapy; Neurological Disorders; Huntington Disease; Batten-disease; Virtual Visits
ISSN (print) / ISBN 1553-7366
e-ISSN 1553-7374
Journal PLoS Pathogens
Quellenangaben Volume: 14, Issue: 4, Pages: , Article Number: e1006991 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place 233 Spring St, New York, Ny 10013 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)