PMID- 10662796
OWN - NLM
STAT- MEDLINE
DCOM- 20000418
LR  - 20190508
IS  - 0022-1007 (Print)
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Linking)
VI  - 191
IP  - 3
DP  - 2000 Feb 7
TI  - Efficient generation of a hepatitis B virus cytotoxic T lymphocyte epitope 
      requires the structural features of immunoproteasomes.
PG  - 503-14
AB  - Interferon (IFN)-gamma-induced cells express the proteasome subunits low 
      molecular weight protein (LMP)2, LMP7, and MECL-1 (multicatalytic endopeptidase 
      complex-like 1), leading to the formation of immunoproteasomes. Although these 
      subunits are thought to optimize MHC class I antigen processing, the extent of 
      their role and the mechanistic aspects involved remain unclear. Herein, we study 
      the proteolytic generation of an human histocompatibility leukocyte antigen 
      (HLA)-Aw68-restricted hepatitis B virus core antigen (HBcAg) cytotoxic T 
      lymphocyte (CTL) epitope that is recognized by peripheral blood lymphocytes from 
      patients with acute self-limited but not chronic hepatitis B virus (HBV). 
      Immunological data suggest that IFN-gamma-induced rather than uninduced HeLa 
      cells process and present the HBV CTL epitope upon infection with 
      HBcAg-expressing vaccinia viruses. Analyses of 20S proteasome digests of 
      synthetic polypeptides covering the antigenic HBcAg peptide demonstrate that only 
      immunoproteasomes efficiently perform the cleavages needed for the liberation of 
      this HBV CTL epitope. Although the concerted presence of the three immunosubunits 
      appears essential, we find that both catalytically active LMP7 and inactive LMP7 
      T1A support CTL epitope generation. We conclude that LMP7 influences the 
      structural features of 20S proteasomes, thereby enhancing the activity of the 
      LMP2 and MECL-1 catalytic sites, which provide cleavage specificity. Thus, LMP7 
      incorporation is of greater functional importance for the generation of an HBV 
      CTL epitope than cleavage specificity.
FAU - Sijts, A J
AU  - Sijts AJ
AD  - Institute of Biochemistry, Charite, Humboldt University Berlin, 10117 Berlin, 
      Germany.
FAU - Ruppert, T
AU  - Ruppert T
FAU - Rehermann, B
AU  - Rehermann B
FAU - Schmidt, M
AU  - Schmidt M
FAU - Koszinowski, U
AU  - Koszinowski U
FAU - Kloetzel, P M
AU  - Kloetzel PM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (EBV-associated membrane antigen, Epstein-Barr virus)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Hepatitis B Core Antigens)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Peptide Fragments)
RN  - 0 (Proteins)
RN  - 0 (Viral Matrix Proteins)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (LMP7 protein)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Cell Line
MH  - Cysteine Endopeptidases/chemistry
MH  - Epitopes, T-Lymphocyte/chemistry/*immunology
MH  - HeLa Cells
MH  - Hepatitis B/immunology
MH  - Hepatitis B Core Antigens/chemistry/*immunology
MH  - Humans
MH  - Interferon-gamma/pharmacology
MH  - Kinetics
MH  - Major Histocompatibility Complex
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Molecular Sequence Data
MH  - Multienzyme Complexes/chemistry
MH  - Peptide Fragments/chemistry
MH  - Proteasome Endopeptidase Complex
MH  - Proteins
MH  - Structure-Activity Relationship
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Transfection
MH  - Viral Matrix Proteins
PMC - PMC2195811
EDAT- 2000/02/09 09:00
MHDA- 2000/06/03 09:00
PMCR- 2000/08/07
CRDT- 2000/02/09 09:00
PHST- 2000/02/09 09:00 [pubmed]
PHST- 2000/06/03 09:00 [medline]
PHST- 2000/02/09 09:00 [entrez]
PHST- 2000/08/07 00:00 [pmc-release]
AID - 99-0815 [pii]
AID - 10.1084/jem.191.3.503 [doi]
PST - ppublish
SO  - J Exp Med. 2000 Feb 7;191(3):503-14. doi: 10.1084/jem.191.3.503.