Journal Article

FZJ-2022-01343

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Single MHC‐I Expression Promotes Virus‐Induced Liver Immunopathology

Xu, H. C. ; Huang, J. ; Pandyra, A. A. ; Pandey, P. ; Wang, R. ; Zhang, Z. ; Zhuang, Y. ; Gertzen, C. G. W.FZJ* ; Münk, C. ; Herebian, D. ; Borkhardt, A. ; Recher, M. ; Gohlke, H.FZJ* ; Esposito, I. ; Oberbarnscheidt, M. ; Häussinger, D. ; Lang, K. S. ; Lang, P. A. (Corresponding author)

2022
Wiley Hoboken, NJ

This record in other databases:      

Please use a persistent id in citations: http://hdl.handle.net/2128/31378  doi:10.1002/hep4.1913

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.

---

Contributing Institute(s):

1. Jülich Supercomputing Center (JSC)
2. Strukturbiochemie (IBI-7)
3. John von Neumann - Institut für Computing (NIC)
4. Bioinformatik (IBG-4)

Research Program(s):

1. 5111 - Domain-Specific Simulation & Data Life Cycle Labs (SDLs) and Research Groups (POF4-511) (POF4-511)
2. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)
3. Forschergruppe Gohlke (hkf7_20200501) (hkf7_20200501)

Appears in the scientific report 2022

---

Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Web of Science Core Collection

---