Open AccessHLA-B locus products resist degradation by the human cytomegalovirus immunoevasin US11
Author(s) -
Cosima Zimmermann,
Daniel J. Kowalewski,
Liane Bauersfeld,
Andreas Hildenbrand,
Carolin Gerke,
Magdalena Schwarzmüller,
Vu Thuy Khanh LeTrilling,
Stefan Stevanović,
Hartmut Hengel,
Frank Momburg,
Anne Halenius
Publication year - 2019
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1008040
Subject(s) - human leukocyte antigen , mhc class i , biology , hla a , cd8 , major histocompatibility complex , locus (genetics) , microbiology and biotechnology , virology , chemistry , genetics , immune system , gene , antigen
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 β 2 m 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.