Please use this identifier to cite or link to this item:
http://dx.doi.org/10.25673/85848
Title: | Viral immune evasins impact antigen presentation by allele-specific trapping of MHC I at the peptide-loading complex |
Author(s): | Sethumadhavan, Sunesh Barth, Marie Spaapen, Robbert M. Schmidt, Carla Trowitzsch, Simon Tampé, Robert |
Issue Date: | 2022 |
Type: | Article |
Language: | English |
Abstract: | Major histocompatibility complex class I (MHC I) molecules present antigenic peptides to cytotoxic T cells to eliminate infected or cancerous cells. The transporter associated with antigen processing (TAP) shuttles proteasomally generated peptides into the ER for MHC I loading. As central part of the peptide-loading complex (PLC), TAP is targeted by viral factors, which inhibit peptide supply and thereby impact MHC I-mediated immune responses. However, it is still poorly understood how antigen presentation via different MHC I allotypes is affected by TAP inhibition. Here, we show that conditional expression of herpes simplex viral ICP47 suppresses surface presentation of HLA-A and HLA-C, but not of HLA-B, while the human cytomegaloviral US6 reduces surface levels of all MHC I allotypes. This marked difference in HLA-B antigen presentation is echoed by an enrichment of HLA-B allomorphs at US6-arrested PLC in comparison to ICP47-PLC. Although both viral factors prevent TAP-mediated peptide supply, our data imply that MHC I allomorphs favor different conformationally arrested states of the PLC, leading to differential downregulation of MHC I surface presentation. These findings will help understand MHC I biology in general and will even advance the targeted treatment of infections depending on patients’ allotypes. |
URI: | https://opendata.uni-halle.de//handle/1981185920/87800 http://dx.doi.org/10.25673/85848 |
Open Access: | Open access publication |
License: | (CC BY 4.0) Creative Commons Attribution 4.0 |
Sponsor/Funder: | Publikationsfonds MLU |
Journal Title: | Scientific reports |
Publisher: | Macmillan Publishers Limited, part of Springer Nature |
Publisher Place: | [London] |
Volume: | 12 |
Original Publication: | 10.1038/s41598-022-05000-9 |
Appears in Collections: | Open Access Publikationen der MLU |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
s41598-022-05000-9.pdf | 3.09 MB | Adobe PDF | View/Open |