PMID- 25522880
OWN - NLM
STAT- MEDLINE
DCOM- 20150320
LR  - 20150110
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 456
IP  - 3
DP  - 2015 Jan 16
TI  - A cyclic peptide accelerates the loading of peptide antigens in major 
      histocompatibility complex class II molecules.
PG  - 774-9
LID - S0006-291X(14)02213-X [pii]
LID - 10.1016/j.bbrc.2014.12.047 [doi]
AB  - Major histocompatibility complex (MHC)-loading enhancers (MLE) have recently 
      attracted attention because of their ability to enhance the efficacy of peptide 
      immunotherapeutics. As small molecular weight compounds, they influence the 
      loading of peptides in MHC molecules by converting them from a non-receptive to a 
      receptive state. Herein, we report a 14-mer cyclic peptide 1 (CP-1) as a new 
      class of MLE-peptide. This peptide was used to investigate its loading on human 
      leukocyte antigen (HLA)-DR molecules. It was found that CP-1 strongly accelerates 
      peptide-loading on both soluble and cell surface HLA-DR molecules in a 
      dose-dependent manner. The effect was evident for all subsets of HLA-DR tested, 
      including HLA-DRB1*1501, indicating that it acts independently of P1-pocket size, 
      which is the canonical MLE-binding site. Importantly, increased peptide-loading 
      by CP-1 was correlated with improved CD4(+) T cell responses in vitro, while 
      propidium iodide staining indicated low peptide-induced cytotoxicity. Thus, this 
      study revealed a new class of peptide-based enhancers that catalyze 
      peptide-loading by allosteric interactions with MHC molecules. Because of its low 
      cellular cytotoxicity and high MLE activity, it may be useful in stimulating 
      antigen-specific T cell responses for therapeutic purposes.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Afridi, Saifullah
AU  - Afridi S
AD  - Dr. Panjwani Center for Molecular Medicine and Drug Research, International 
      Center for Chemical and Biological Sciences, University of Karachi, Karachi 
      75270, Pakistan.
FAU - Shaheen, Farzana
AU  - Shaheen F
AD  - H.E.J. Research Institute of Chemistry, International Center for Chemical and 
      Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
FAU - Roetzschke, Olaf
AU  - Roetzschke O
AD  - Singapore Immunology Network, Agency for Science, Technology and Research, 
      Singapore 138648, Singapore.
FAU - Shah, Zafar Ali
AU  - Shah ZA
AD  - H.E.J. Research Institute of Chemistry, International Center for Chemical and 
      Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
FAU - Abbas, Syed Comail
AU  - Abbas SC
AD  - H.E.J. Research Institute of Chemistry, International Center for Chemical and 
      Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
FAU - Siraj, Rizwana
AU  - Siraj R
AD  - Dr. Panjwani Center for Molecular Medicine and Drug Research, International 
      Center for Chemical and Biological Sciences, University of Karachi, Karachi 
      75270, Pakistan.
FAU - Makhmoor, Talat
AU  - Makhmoor T
AD  - Dr. Panjwani Center for Molecular Medicine and Drug Research, International 
      Center for Chemical and Biological Sciences, University of Karachi, Karachi 
      75270, Pakistan. Electronic address: makhmoor@iccs.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141215
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Peptides, Cyclic)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - HLA-DR Antigens/chemistry/*immunology
MH  - Humans
MH  - Immunotherapy
MH  - Mice
MH  - NIH 3T3 Cells
MH  - Peptides, Cyclic/chemistry/*immunology
OTO - NOTNLM
OT  - CD4(+) T cell responses
OT  - Cyclic peptide
OT  - HLA-DR1*0101
OT  - MHC class II molecules
OT  - MHC-loading enhancer
EDAT- 2014/12/20 06:00
MHDA- 2015/03/21 06:00
CRDT- 2014/12/20 06:00
PHST- 2014/12/02 00:00 [received]
PHST- 2014/12/09 00:00 [accepted]
PHST- 2014/12/20 06:00 [entrez]
PHST- 2014/12/20 06:00 [pubmed]
PHST- 2015/03/21 06:00 [medline]
AID - S0006-291X(14)02213-X [pii]
AID - 10.1016/j.bbrc.2014.12.047 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2015 Jan 16;456(3):774-9. doi: 
      10.1016/j.bbrc.2014.12.047. Epub 2014 Dec 15.