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Ameres, S. ; Mautner, J. ; Schlott, F. ; Neuenhahn, M. ; Busch, D.H. ; Plachter, B.* ; Moosmann, A.

Presentation of an immunodominant immediate-early CD8+ T cell epitope resists human cytomegalovirus immunoevasion.

PLoS Pathog. 9:e1003383 (2013)
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Control of human cytomegalovirus (HCMV) depends on CD8+ T cell responses that are shaped by an individual's repertoire of MHC molecules. MHC class I presentation is modulated by a set of HCMV-encoded proteins. Here we show that HCMV immunoevasins differentially impair T cell recognition of epitopes from the same viral antigen, immediate-early 1 (IE-1), that are presented by different MHC class I allotypes. In the presence of immunoevasins, HLA-A- and HLA-B-restricted T cell clones were ineffective, but HLA-C*0702-restricted T cell clones recognized and killed infected cells. Resistance of HLA-C*0702 to viral immunoevasins US2 and US11 was mediated by the alpha3 domain and C-terminal region of the HLA heavy chain. In healthy donors, HLA-C*0702-restricted T cells dominated the T cell response to IE-1. The same HLA-C allotype specifically protected infected cells from attack by NK cells that expressed a corresponding HLA-C-specific KIR. Thus, allotype-specific viral immunoevasion allows HCMV to escape control by NK cells and HLA-A- and HLA-B-restricted T cells, while the virus becomes selectively vulnerable to an immunodominant population of HLA-C-restricted T cells. Our work identifies a T cell population that may be of particular efficiency in HCMV-specific immunotherapy.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Major Histocompatibility Complex ; Class-i Molecules ; Cd8(+) T-cells ; Immune Evasion Proteins ; Natural-killer-cells ; Hla Class-i ; Down-regulation ; Endoplasmic-reticulum ; Adoptive Transfer ; Transplant Recipients
Language english
Publication Year 2013
HGF-reported in Year 2013
ISSN (print) / ISBN 1553-7366
e-ISSN 1553-7374
Journal PLoS Pathogens
Quellenangaben Volume: 9, Issue: 5, Pages: , Article Number: e1003383 Supplement: ,
Publisher Public Library of Science (PLoS)
Reviewing status Peer reviewed
Institute(s) CCG Immunooncology (AGV-KIO)
Institute of Molecular Immunology (IMI)
CCG Pediatric Tumor Immunology (AGV-KPT)
Research Unit Gene Vector (AGV)
Institute of Virology (VIRO)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30203 - Molecular Targets and Therapies
Research field(s) Immune Response and Infection
PSP Element(s) G-521700-001
G-501790-003
G-501790-002
G-520900-001
G-501500-001
G-520100-001
G-501790-001
PubMed ID 23717207
DOI 10.1371/journal.ppat.1003383
WOS ID WOS:000320032800055
Erfassungsdatum 2013-07-12
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