PMID- 22306902
OWN - NLM
STAT- MEDLINE
DCOM- 20120503
LR  - 20120206
IS  - 1537-4513 (Electronic)
IS  - 1524-9557 (Linking)
VI  - 35
IP  - 2
DP  - 2012 Feb-Mar
TI  - Efficiency and mechanism of antigen-specific CD8+ T-cell activation using 
      synthetic long peptides.
PG  - 142-53
LID - 10.1097/CJI.0b013e318243f1ed [doi]
AB  - Synthetic long peptides that contain immunogenic T-cell epitopes have been used 
      to induce activation of antigen-specific CD8 T cells in vitro for immune 
      monitoring or adoptive transfer, or in vivo after peptide vaccination. However, 
      the efficiency and mechanisms of presentation of exogenous long peptides in human 
      leukocyte antigen (HLA) class I remain to be elucidated. In this study, we 
      demonstrated that the efficiency of antigen-specific CD8 T-cell activation using 
      extended peptide variants of common viral epitopes is variable. We demonstrated 
      that processing and HLA class I presentation of the long peptides were not 
      dependent on the proteasome and transporter associated with antigen processing, 
      illustrating that the classic route of HLA class I presentation was not required 
      for activation of specific CD8 T cells by exogenous synthetic long peptides. 
      Although long peptides were shown to bind to the relevant HLA class I molecules, 
      peptide trimming was likely to be essential for optimal HLA class I presentation 
      and T-cell activation. As the proteasome was not required for processing of 
      exogenous peptides, it is very likely that peptide trimming was mediated by 
      peptidases, which may be located extracellularly at the cell surface, in the 
      cytosol, endoplasmic reticulum, or in endosomal and lysosomal compartments. 
      Furthermore, the results suggested that processing of the correct minimal 
      peptides was facilitated by binding in HLA class I molecules. This mechanism of 
      HLA-guided processing may be important in HLA class I presentation of exogenous 
      long peptides to induce activation of specific CD8 T cells.
FAU - Zandvliet, Maarten L
AU  - Zandvliet ML
AD  - Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 
      Leiden, The Netherlands. m.l.zandvliet@lumc.nl
FAU - Kester, Michel G D
AU  - Kester MG
FAU - van Liempt, Ellis
AU  - van Liempt E
FAU - de Ru, Arnoud H
AU  - de Ru AH
FAU - van Veelen, Peter A
AU  - van Veelen PA
FAU - Griffioen, Marieke
AU  - Griffioen M
FAU - Guchelaar, Henk-Jan
AU  - Guchelaar HJ
FAU - Falkenburg, J H Frederik
AU  - Falkenburg JH
FAU - Meij, Pauline
AU  - Meij P
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Peptides)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antigen Presentation/*immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Chromatography, High Pressure Liquid
MH  - Epitopes, T-Lymphocyte/chemistry/*immunology
MH  - Histocompatibility Antigens Class I/immunology
MH  - Humans
MH  - Lymphocyte Activation/*immunology
MH  - Mass Spectrometry
MH  - Molecular Sequence Data
MH  - Peptides/chemistry/*immunology
EDAT- 2012/02/07 06:00
MHDA- 2012/05/04 06:00
CRDT- 2012/02/07 06:00
PHST- 2012/02/07 06:00 [entrez]
PHST- 2012/02/07 06:00 [pubmed]
PHST- 2012/05/04 06:00 [medline]
AID - 00002371-201202000-00005 [pii]
AID - 10.1097/CJI.0b013e318243f1ed [doi]
PST - ppublish
SO  - J Immunother. 2012 Feb-Mar;35(2):142-53. doi: 10.1097/CJI.0b013e318243f1ed.