PMID- 25454619
OWN - NLM
STAT- MEDLINE
DCOM- 20150730
LR  - 20201209
IS  - 1879-1166 (Electronic)
IS  - 0198-8859 (Linking)
VI  - 75
IP  - 12
DP  - 2014 Dec
TI  - Tregitope: Immunomodulation powerhouse.
PG  - 1139-46
LID - S0198-8859(14)00477-7 [pii]
LID - 10.1016/j.humimm.2014.10.012 [doi]
AB  - IVIG is frequently used in the 'pre-conditioning' regimens for higher risk 
      transplants; its effects are attributed in part to induction of Tregs. We have 
      identified regulatory T cell (Treg) epitopes, now known as Tregitopes, in IgG, 
      the main component of intravenous immunoglobulin therapy (IVIg). Tregitopes 
      provide one explanation for the expansion and activation of Treg cells following 
      IVIg treatment. Tregitopes are peptides that exhibit high affinity binding to 
      multiple human HLA Class II DR; they are conserved across IgG isotypes and 
      mammalian species. In vitro and in vivo, for human PBMC and in animal models, 
      Tregitopes activate Tregs. Studies to delineate the mechanism of action have 
      shown that Tregitopes' effects are very similar to IVIg in vitro. Here we 
      demonstrate that Tregitopes induce Tregs to produce IL-10, leading to modulation 
      of dendritic cell phenotype (down-regulation of Class II, CD80 and CD86 and 
      up-regulation of ILT3), and describe the effects of Tregitopes in the 
      ABM-TCR-transgenic skin transplantation model. The discovery of Tregitopes in IgG 
      and other autologous proteins may contribute to improved understanding of the 
      mechanism of action of IVIg and lead to the application of these powerful 
      immunomodulators to improve transplantation success and suppress autoimmune 
      disease, in the future.
CI  - Copyright (c) 2014 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Cousens, Leslie
AU  - Cousens L
AD  - EpiVax, Inc., Providence, RI, USA.
FAU - Najafian, Nader
AU  - Najafian N
AD  - Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; 
      Cleveland Clinic, Weston, FL, USA.
FAU - Martin, William D
AU  - Martin WD
AD  - EpiVax, Inc., Providence, RI, USA.
FAU - De Groot, Anne S
AU  - De Groot AS
AD  - EpiVax, Inc., Providence, RI, USA; Institute for Immunology and Informatics, 
      University of Rhode Island, Providence, RI, USA. Electronic address: 
      AnnieD@EpiVax.com.
LA  - eng
PT  - Journal Article
DEP - 20141022
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (B7-1 Antigen)
RN  - 0 (B7-2 Antigen)
RN  - 0 (CD86 protein, human)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (IL10 protein, human)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (LILRB4 protein, human)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Immunologic)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Animals
MH  - B7-1 Antigen/biosynthesis
MH  - B7-2 Antigen/biosynthesis
MH  - Dendritic Cells/immunology
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Female
MH  - HLA-DR Antigens/immunology
MH  - Humans
MH  - Immune Tolerance/immunology
MH  - Immunization, Passive
MH  - Immunoglobulin G/*immunology
MH  - Immunoglobulins, Intravenous
MH  - Immunomodulation
MH  - Interleukin-10/biosynthesis
MH  - Leukocytes, Mononuclear/immunology
MH  - Lymphocyte Activation/*immunology
MH  - Membrane Glycoproteins
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Receptors, Cell Surface/biosynthesis
MH  - Receptors, Immunologic
MH  - Skin Transplantation
MH  - T-Lymphocytes, Regulatory/*immunology
MH  - Transplantation Tolerance/*immunology
OTO - NOTNLM
OT  - IVIg
OT  - Tolerance
OT  - Transplantation
OT  - Treg
OT  - Tregitope
EDAT- 2014/12/03 06:00
MHDA- 2015/08/01 06:00
CRDT- 2014/12/03 06:00
PHST- 2014/07/03 00:00 [received]
PHST- 2014/07/07 00:00 [revised]
PHST- 2014/10/09 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/08/01 06:00 [medline]
AID - S0198-8859(14)00477-7 [pii]
AID - 10.1016/j.humimm.2014.10.012 [doi]
PST - ppublish
SO  - Hum Immunol. 2014 Dec;75(12):1139-46. doi: 10.1016/j.humimm.2014.10.012. Epub 
      2014 Oct 22.