PMID- 35602060
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230904
IS  - 1664-302X (Print)
IS  - 1664-302X (Electronic)
IS  - 1664-302X (Linking)
VI  - 13
DP  - 2022
TI  - Endoplasmic Reticulum Aminopeptidase 1 Is Involved in Anti-viral Immune Response 
      of Hepatitis B Virus by Trimming Hepatitis B Core Antigen to Generate 9-Mers 
      Peptides.
PG  - 829241
LID - 10.3389/fmicb.2022.829241 [doi]
LID - 829241
AB  - Endoplasmic reticulum aminopeptidase 1 (ERAP1) is a processing enzyme of 
      antigenic peptides presented to major histocompatibility complex (MHC) class I 
      molecules. ERAP1-dependent trimming of epitope repertoire determines an efficacy 
      of adoptive CD8(+) T-cell responses in several viral diseases; however, its role 
      in hepatitis B virus (HBV) infection remains unknown. Here, we show that the 
      serum level of ERAP1 in patients with chronic hepatitis B (CHB) (n = 128) was 
      significantly higher than that of healthy controls (n = 44) (8.78 +/- 1.82 vs. 3.52 
      +/- 1.61, p < 0.001). Furthermore, peripheral ERAP1 level is moderately correlated 
      with HBV DNA level in patients with CHB (r = 0.731, p < 0.001). HBV-transfected 
      HepG2.2.15 cells had substantially increased ERAP1 expression and secretion than 
      the germline HepG2 cells (p < 0.001). The co-culture of ERAP1-specific inhibitor 
      ERAP1-IN-1 pretreated HepG2.2.15 cells or ERAP1 knockdown HepG2.2.15 cells with 
      CD8(+) T cells led to 14-24% inhibition of the proliferation of CD8(+) T cells. 
      Finally, liquid chromatography tandem mass spectrometry (LC-MS/MS) test 
      demonstrated that ERAP1-IN-1 blocks completely the production of a 9-mers peptide 
      (30-38, LLDTASALY) derived from Hepatitis B core antigen (HBcAg). The predictive 
      analysis by NetMHCpan-4.1 server showed that human leukocyte antigen 
      (HLA)-C*04:01 is a strong binder for the 9-mers peptide in HepG2.2.15 cells. 
      Taken together, our results demonstrated that ERAP1 trims HBcAg to produce 9-mers 
      LLDTASALY peptides for binding onto HLA-C*04:01 in HepG2.2.15 cells, facilitating 
      the potential activation of CD8(+) T cells.
CI  - Copyright (c) 2022 Liu, Hu, Huang, Wang, Wang, Pan and Chen.
FAU - Liu, Huanhuan
AU  - Liu H
AD  - Department of Laboratory Medicine, Second Hospital of Anhui Medical University, 
      Hefei, China.
FAU - Hu, Bingqi
AU  - Hu B
AD  - Department of Laboratory Medicine, Second Hospital of Anhui Medical University, 
      Hefei, China.
FAU - Huang, Junfeng
AU  - Huang J
AD  - Department of Laboratory Medicine, Second Hospital of Anhui Medical University, 
      Hefei, China.
FAU - Wang, Qin
AU  - Wang Q
AD  - Department of Laboratory Medicine, Second Hospital of Anhui Medical University, 
      Hefei, China.
FAU - Wang, Feier
AU  - Wang F
AD  - Department of Epidemiology and Biostatistics, School of Public Health, Anhui 
      Medical University, Hefei, China.
FAU - Pan, Faming
AU  - Pan F
AD  - Department of Epidemiology and Biostatistics, School of Public Health, Anhui 
      Medical University, Hefei, China.
FAU - Chen, Liwen
AU  - Chen L
AD  - Department of Laboratory Medicine, Second Hospital of Anhui Medical University, 
      Hefei, China.
LA  - eng
PT  - Journal Article
DEP - 20220504
PL  - Switzerland
TA  - Front Microbiol
JT  - Frontiers in microbiology
JID - 101548977
EIN - Front Microbiol. 2023 Aug 18;14:1273875. PMID: 37664124
PMC - PMC9115554
OTO - NOTNLM
OT  - antigen presentation
OT  - endoplasmic reticulum aminopeptidase 1
OT  - hepatitis B
OT  - immune response
OT  - major histocompatibility complex class I
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/05/24 06:00
MHDA- 2022/05/24 06:01
PMCR- 2022/05/04
CRDT- 2022/05/23 04:21
PHST- 2021/12/05 00:00 [received]
PHST- 2022/03/17 00:00 [accepted]
PHST- 2022/05/23 04:21 [entrez]
PHST- 2022/05/24 06:00 [pubmed]
PHST- 2022/05/24 06:01 [medline]
PHST- 2022/05/04 00:00 [pmc-release]
AID - 10.3389/fmicb.2022.829241 [doi]
PST - epublish
SO  - Front Microbiol. 2022 May 4;13:829241. doi: 10.3389/fmicb.2022.829241. 
      eCollection 2022.