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@ARTICLE{Xu:906279,
author = {Xu, Haifeng C. and Huang, Jun and Pandyra, Aleksandra A.
and Pandey, Piyush and Wang, Ruifeng and Zhang, Zeli and
Zhuang, Yuan and Gertzen, Christoph G. W. and Münk, Carsten
and Herebian, Diran and Borkhardt, Arndt and Recher, Mike
and Gohlke, Holger and Esposito, Irene and Oberbarnscheidt,
Martin and Häussinger, Dieter and Lang, Karl S. and Lang,
Philipp A.},
title = {{S}ingle {MHC}‐{I} {E}xpression {P}romotes
{V}irus‐{I}nduced {L}iver {I}mmunopathology},
journal = {Hepatology communications},
volume = {6},
number = {7},
issn = {2471-254X},
address = {Hoboken, NJ},
publisher = {Wiley},
reportid = {FZJ-2022-01343},
pages = {1620-1633},
year = {2022},
abstract = {Major histocompatibility complex I (MHC-I) molecules
present epitopes on the cellular surface of
antigen-presenting cells to prime cytotoxic clusters of
differentiation 8 (CD8)+ T cells (CTLs), which then identify
and eliminate other cells such as virus-infected cells
bearing the antigen. Human hepatitis virus cohort studies
have previously identified MHC-I molecules as promising
predictors of viral clearance. However, the underlying
functional significance of these predictions is not fully
understood. Here, we show that expression of single MHC-I
isomers promotes virus-induced liver immunopathology.
Specifically, using the lymphocytic choriomeningitis virus
(LCMV) model system, we found MHC-I proteins to be highly
up-regulated during infection. Deletion of one of the two
MHC-I isomers histocompatibility antigen 2 (H2)–Db or
H2-Kb in C57Bl/6 mice resulted in CTL activation recognizing
the remaining MHC-I with LCMV epitopes in increased paucity.
This increased CTL response resulted in hepatocyte death,
increased caspase activation, and severe metabolic changes
in liver tissue following infection with LCMV. Moreover,
depletion of CTLs abolished LCMV-induced pathology in these
mice with resulting viral persistence. In turn, natural
killer (NK) cell depletion further increased antiviral CTL
immunity and clearance of LCMV even in the presence of a
single MHC-I isomer. Conclusion: Our results suggest that
uniform MHC-I molecule expression promotes enhanced CTL
immunity during viral infection and contributes to increased
CTL-mediated liver cell damage that was alleviated by CD8 or
NK cell depletion.},
cin = {JSC / IBI-7 / NIC / IBG-4},
ddc = {610},
cid = {I:(DE-Juel1)JSC-20090406 / I:(DE-Juel1)IBI-7-20200312 /
I:(DE-Juel1)NIC-20090406 / I:(DE-Juel1)IBG-4-20200403},
pnm = {5111 - Domain-Specific Simulation $\&$ Data Life Cycle Labs
(SDLs) and Research Groups (POF4-511) / 5241 - Molecular
Information Processing in Cellular Systems (POF4-524) /
Forschergruppe Gohlke $(hkf7_20200501)$},
pid = {G:(DE-HGF)POF4-5111 / G:(DE-HGF)POF4-5241 /
$G:(DE-Juel1)hkf7_20200501$},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35166071},
UT = {WOS:000754878800001},
doi = {10.1002/hep4.1913},
url = {https://juser.fz-juelich.de/record/906279},
}