PMID- 15618468
OWN - NLM
STAT- MEDLINE
DCOM- 20050513
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 105
IP  - 8
DP  - 2005 Apr 15
TI  - Processing and presentation of HLA class I and II epitopes by dendritic cells 
      after transfection with in vitro-transcribed MUC1 RNA.
PG  - 3199-205
AB  - RNA transfection of dendritic cells (DCs) was shown to be highly efficient in 
      eliciting CD8+ and CD4+ T-cell responses. However, antigen presentation pathways 
      involved in generation of human leukocyte antigen (HLA) class I and class II 
      peptides have remained elusive. To analyze this we incubated mucin 1 (MUC1) 
      RNA-transfected DCs with compounds known to inhibit HLA class I presentation and 
      used these cells in chromium 51 (51Cr)-release assays. As effectors, we used 
      cytotoxic T lymphocyte (CTL) lines specific for the MUC1 peptides M1.1 and M1.2. 
      We observed that the presentation of HLA-A*02 epitopes is inhibited by brefeldin 
      A and lactacystin. To determine the requirement of a functional transporter 
      associated with antigen processing (TAP), we cotransfected DCs with MUC1 and 
      infected cell peptide 47 (ICP47) RNA. ICP47 could only inhibit the presentation 
      of the M1.1 but not the M1.2 peptide, indicating that this epitope derived from 
      the signal sequence is presented independently of TAP. Cocultivation of MUC1 
      RNA-transfected DCs with MUC1-specific CD4+ T lymphocytes revealed that the 
      presentation of HLA class II peptides is sensitive to proteasomal inhibitors and 
      brefeldin A. Furthermore, the presentation pathway requires lysosomal and 
      endosomal processing and is mediated by autophagy. Our results demonstrate that 
      the efficient presentation of cytosolic proteins on major histocompatibility 
      complex (MHC) class II combines the proteolytic and lysosomal pathways.
FAU - Dorfel, Daniela
AU  - Dorfel D
AD  - Department of Hematology, Oncology and Immunology, University of Tubingen, 
      Tubingen, Germany.
FAU - Appel, Silke
AU  - Appel S
FAU - Grunebach, Frank
AU  - Grunebach F
FAU - Weck, Markus M
AU  - Weck MM
FAU - Muller, Martin R
AU  - Muller MR
FAU - Heine, Annkristin
AU  - Heine A
FAU - Brossart, Peter
AU  - Brossart P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20041223
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Epitopes)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (ICP47 protein, Herpes simplex virus)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Mucin-1)
RN  - 0 (Viral Proteins)
RN  - 63231-63-0 (RNA)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Antigen Presentation/*physiology
MH  - Autophagy/immunology
MH  - Cytosol/immunology
MH  - Dendritic Cells/*immunology
MH  - Electroporation
MH  - Endosomes/immunology
MH  - Epitopes/immunology
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Histocompatibility Antigens Class II/*immunology
MH  - Humans
MH  - Immediate-Early Proteins/pharmacology
MH  - In Vitro Techniques
MH  - Mucin-1/*genetics
MH  - Proteasome Endopeptidase Complex/immunology
MH  - RNA
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Transcription, Genetic
MH  - Transfection
MH  - Viral Proteins/pharmacology
EDAT- 2004/12/25 09:00
MHDA- 2005/05/14 09:00
CRDT- 2004/12/25 09:00
PHST- 2004/12/25 09:00 [pubmed]
PHST- 2005/05/14 09:00 [medline]
PHST- 2004/12/25 09:00 [entrez]
AID - S0006-4971(20)45614-9 [pii]
AID - 10.1182/blood-2004-09-3556 [doi]
PST - ppublish
SO  - Blood. 2005 Apr 15;105(8):3199-205. doi: 10.1182/blood-2004-09-3556. Epub 2004 
      Dec 23.