TY  - JOUR
A1  - Sethumadhavan, Sunesh
A1  - Barth, Marie
A1  - Spaapen, Robbert M.
A1  - Schmidt, Carla
A1  - Trowitzsch, Simon
A1  - Tampé, Robert
T1  - Viral immune evasins impact antigen presentation by allele-specific trapping of MHC I at the peptide-loading complex
T2  - Scientific reports
N2  - 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.
KW  - Antigen processing and presentation
KW  - Biochemistry
KW  - Biological techniques
KW  - Cell biology
KW  - Immune evasion
KW  - Immunochemistry
KW  - Immunology
KW  - Isolation, separation and purification
KW  - Mass spectrometry
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/69634
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-696342
SN  - 2045-2322
N1  - The work was supported by the Landsteiner Foundation for Blood Transfusion Research (LSBR 1842F; R.M.S.), the Dutch Research Council (NWO-VIDI 91719369 to R.M.S.), the German Research Foundation (CRC 807/P16 and Reinhart Koselleck Project TA 157/12-1 to R.T.), as well as by the European Research Council (ERC Advanced Grant 798121 to R.T.).
N1  - Open Access funding enabled and organized by Projekt DEAL.
VL  - 12
IS  - art. 1516
SP  - 1
EP  - 11
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  -