Presentation of an Immunodominant Immediate-Early CD8+ T Cell Epitope Resists Human Cytomegalovirus Immunoevasion

PLoS Pathogens

Andreas Moosmann¹  Stefanie Ameres²  Michael Neuenhahn³  Fabian Schlott⁴  Josef Mautner⁴  Dirk H. Busch⁴  Bodo Plachter⁵ 

[1] Clinical Cooperation Group Immune Monitoring, Helmholtz Zentrum München and Technische Universität München, Munich, Germany;Clinical Cooperation Group Immunooncology, Department of Medicine III, Klinikum der Universität München, and Department of Gene Vectors, Helmholtz Zentrum München, Munich, Germany;Clinical Cooperation Group Pediatric Tumor Immunology, Helmholtz Zentrum München, and Children's Hospital, Technische Universität München, Munich, Germany;DZIF – German Center for Infection Research, Munich, Germany;Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany

关键词: T cells;    Fibroblasts;    Cytotoxic T cells;    NK cells;    Major histocompatibility complex;    Antigen presentation;    Enzyme-linked immunoassays;    MHC class I genes;   

DOI  :  10.1371/journal.ppat.1003383

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY