Unknown

Dataset Information

0

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


ABSTRACT: 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 ?2m 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.

SUBMITTER: Zimmermann C 

PROVIDER: S-EPMC6764698 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications


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  ...[more]

Similar Datasets

| S-EPMC4899442 | biostudies-literature
| S-EPMC3741148 | biostudies-literature
| S-EPMC2840211 | biostudies-literature
| S-EPMC2645836 | biostudies-other
| S-EPMC4032930 | biostudies-literature
| S-EPMC7296005 | biostudies-literature
| S-EPMC3557549 | biostudies-literature
| S-EPMC9701276 | biostudies-literature
| S-EPMC3557549 | biostudies-other
| S-EPMC4504510 | biostudies-literature