HLA-B locus products resist degradation by the human cytomegalovirus immunoevasin US11

English version

Autoři: Cosima Zimmermann ^aff001; Daniel Kowalewski ^aff003; Liane Bauersfeld ^aff001; Andreas Hildenbrand ^aff001; Carolin Gerke ^aff001; Magdalena Schwarzmüller ^aff001; Vu Thuy Khanh Le-Trilling ^aff006; Stefan Stevanovic ^aff003; Hartmut Hengel ^aff001; Frank Momburg ^aff007; Anne Halenius ^aff001
Působiště autorů: Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany ^aff001; Faculty of Medicine, University of Freiburg, Freiburg, Germany ^aff002; Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Germany ^aff003; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany ^aff004; Faculty of Biology, University of Freiburg, Freiburg, Germany ^aff005; Institute for Virology, University Duisburg-Essen, Essen, Germany ^aff006; Clinical Cooperation Unit Applied Tumor Immunity, Antigen Presentation and T/NK Cell Activation Group, German Cancer Research Center, Heidelberg, Germany ^aff007
Vyšlo v časopise: HLA-B locus products resist degradation by the human cytomegalovirus immunoevasin US11. PLoS Pathog 15(9): e1008040. doi:10.1371/journal.ppat.1008040
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008040

Souhrn

To escape CD8+ T-cell immunity, human cytomegalovirus (HCMV) US11 redirects MHC-I for rapid ER-associated proteolytic degradation (ERAD). In humans, classical MHC-I molecules are encoded by the highly polymorphic HLA-A, -B and -C gene loci. While HLA-C resists US11 degradation, the specificity for HLA-A and HLA-B products has not been systematically studied. In this study we analyzed the MHC-I peptide ligands in HCMV-infected cells. A US11-dependent loss of HLA-A ligands was observed, but not of HLA-B. We revealed a general ability of HLA-B to assemble with β₂m and exit from the ER in the presence of US11. Surprisingly, a low-complexity region between the signal peptide sequence and the Ig-like domain of US11, was necessary to form a stable interaction with assembled MHC-I and, moreover, this region was also responsible for changing the pool of HLA-B ligands. Our data suggest a two-pronged strategy by US11 to escape CD8+ T-cell immunity, firstly, by degrading HLA-A molecules, and secondly, by manipulating the HLA-B ligandome.

Klíčová slova:

Research and analysis methods – Biological cultures – Cell lines – HeLa cells – Cell cultures – Cultured tumor cells – Precipitation techniques – Immunoprecipitation – Co-immunoprecipitation – Spectrum analysis techniques – Spectrophotometry – Cytophotometry – Flow cytometry – Biology and life sciences – Organisms – Viruses – DNA viruses – Herpesviruses – Human cytomegalovirus – Microbiology – Medical microbiology – Microbial pathogens – Viral pathogens – Genetics – Gene expression – Gene regulation – Small interfering RNAs – Biochemistry – Nucleic acids – RNA – Non-coding RNA – Cell biology – Cellular types – Animal cells – Connective tissue cells – Fibroblasts – Blood cells – White blood cells – T cells – Cytotoxic T cells – Immune cells – Anatomy – Biological tissue – Connective tissue – Medicine and health sciences – Pathology and laboratory medicine – Pathogens – Immunology

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