Effect of Hsp70-peptide complexes generated in vivo on modulation EAE

2001 ◽  
pp. 227-230 ◽  
Author(s):  
Grazyna Galazka ◽  
Agata Walczak ◽  
Tomasz Berkowicz ◽  
Krzysztof Selmaj
Keyword(s):  
Peptide Complexes

Anatomic location and T-cell stimulatory functions of mouse dendritic cell subsets defined by CD4 and CD8 expression

Blood ◽  
2002 ◽  
Vol 99 (6) ◽  
pp. 2084-2093 ◽  
Author(s):  
Alexander D. McLellan ◽  
Michaela Kapp ◽  
Andreas Eggert ◽  
Christian Linden ◽  
Ursula Bommhardt ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Antigen Expression ◽  
Cell Receptor ◽  
In Vitro Assays ◽  
Peptide Complexes ◽  
Marginal Zones

Abstract Mouse spleen contains CD4+, CD8α+, and CD4−/CD8α− dendritic cells (DCs) in a 2:1:1 ratio. An analysis of 70 surface and cytoplasmic antigens revealed several differences in antigen expression between the 3 subsets. Notably, the Birbeck granule–associated Langerin antigen, as well as CD103 (the mouse homologue of the rat DC marker OX62), were specifically expressed by the CD8α+ DC subset. All DC types were apparent in the T-cell areas as well as in the splenic marginal zones and showed similar migratory capacity in collagen lattices. The 3 DC subtypes stimulated allogeneic CD4+ T cells comparably. However, CD8α+ DCs were very weak stimulators of resting or activated allogeneic CD8+ T cells, even at high stimulator-to-responder ratios, although this defect could be overcome under optimal DC/T cell ratios and peptide concentrations using CD8+ F5 T-cell receptor (TCR)–transgenic T cells. CD8α− or CD8α+DCs presented alloantigens with the same efficiency for lysis by cytotoxic T lymphocytes (CTLs), and their turnover rate of class I–peptide complexes was similar, thus neither an inability to present, nor rapid loss of antigenic complexes from CD8α DCs was responsible for the low allostimulatory capacity of CD8α+ DCs in vitro. Surprisingly, both CD8α+ DCs and CD4−/CD8− DCs efficiently primed minor histocompatibility (H-Y male antigen) cytotoxicity following intravenous injection, whereas CD4+ DCs were weak inducers of CTLs. Thus, the inability of CD8α+ DCs to stimulate CD8+ T cells is limited to certain in vitro assays that must lack certain enhancing signals present during in vivo interaction between CD8α+ DCs and CD8+ T cells.

scholarly journals CD8+Dendritic Cells Use LFA-1 to Capture MHC-Peptide Complexes from Exosomes In Vivo

2007 ◽  
Vol 179 (3) ◽  
pp. 1489-1496 ◽  
Author(s):  
Elodie Segura ◽  
Coralie Guérin ◽  
Nancy Hogg ◽  
Sebastian Amigorena ◽  
Clotilde Théry
Keyword(s):  
Dendritic Cells ◽  
Peptide Complexes

scholarly journals NMR Structure and CD Titration with Metal Cations of Human Prionα2-Helix-Related Peptides

2007 ◽  
Vol 2007 ◽  
pp. 1-9 ◽  
Author(s):  
Luisa Ronga ◽  
Pasquale Palladino ◽  
Gabriella Saviano ◽  
Teodorico Tancredi ◽  
Ettore Benedetti ◽  
...  
Keyword(s):  
Prion Protein ◽  
Point Mutations ◽  
Metal Cations ◽  
Spectroscopic Studies ◽  
Cation Binding ◽  
Protein Domain ◽  
Wild Type ◽  
Peptide Complexes ◽  
Natural Target

The 173–195 segment corresponding to the helix 2 of the C-globular prion protein domain could be one of several “spots” of intrinsic conformational flexibility. In fact, it possesses chameleon conformational behaviour and gathers several disease-associated point mutations. We have performed spectroscopic studies on the wild-type fragment 173–195 and on its D178N mutant dissolved in trifluoroethanol to mimic the in vivo system, both in the presence and in the absence of metal cations. NMR data showed that the structure of the D178N mutant is characterized by two short helices separated by a kink, whereas the wild-type peptide is fully helical. Both peptides retained these structural organizations, as monitored by CD, in the presence of metal cations. NMR spectra were however not in favour of the formation of definite ion-peptide complexes. This agrees with previous evidence that other regions of the prion protein are likely the natural target of metal cation binding.

Rapid Death of Adoptively Transferred T Cells in Acquired Immunodeficiency Syndrome

Blood ◽  
1999 ◽  
Vol 93 (5) ◽  
pp. 1506-1510 ◽  
Author(s):  
Rusung Tan ◽  
Xiaoning Xu ◽  
Graham S. Ogg ◽  
Pokrath Hansasuta ◽  
Tao Dong ◽  
...  
Keyword(s):  
T Cell ◽  
Adoptive Transfer ◽  
Acquired Immunodeficiency Syndrome ◽  
Mononuclear Cells ◽  
Virus Load ◽  
Acquired Immunodeficiency ◽  
Peptide Complexes ◽  
Immunodeficiency Syndrome

Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) probably play the major role in controlling HIV replication. However, the value of adoptive transfer of HIV-specific CTL expanded in vitro to HIV+ patients has been limited: this contrasts with the success of CTL therapy in treating or preventing Epstein-Barr virus and cytomegalovirus disease after bone marrow transplantation (BMT). We investigated the fate of expanded HIV-specific CTL clones in vivo following adoptive transfer to a patient with acquired immunodeficiency syndrome (AIDS). Two autologous CTL clones specific for HIV Gag and Pol were expanded to large numbers (>109) in vitro and infused into an HIV-infected patient whose viral load was rising despite antiretroviral therapy. The fate of one clone was monitored by staining peripheral blood mononuclear cells (PBMCs) with T-cell receptor–specific tetrameric major histocompatibility complex (MHC)-peptide complexes. Although the CTL transfer was well tolerated, there were no significant changes in CD4 and CD8 lymphocyte counts and virus load. By tracking an infused clone using soluble MHC-peptide complexes, we show that cells bearing the Gag-specific T-cell receptors were rapidly eliminated within hours of infusion through apoptosis. Thus, the failure of adoptively transferred HIV-specific CTL to reduce virus load in AIDS may be due to rapid apoptosis of the infused cells, triggered by a number of potential mechanisms. Further trials of adoptive transfer of CTL should take into account the susceptibility of infused cells to in vivo apoptosis.

Efficient in vivo induction of CTL by cell-associated covalent H-2Kd-peptide complexes

1994 ◽  
Vol 171 (1) ◽  
pp. 73-84 ◽  
Author(s):  
Pedro Romero ◽  
Jean-Charles Cerottini ◽  
Immanuel F. Luescher
Keyword(s):  
Peptide Complexes ◽  
In Vivo Induction

scholarly journals Heat Shock Protein–Peptide Complexes, Reconstituted In Vitro, Elicit Peptide-specific Cytotoxic T Lymphocyte Response and Tumor Immunity

1997 ◽  
Vol 186 (8) ◽  
pp. 1315-1322 ◽  
Author(s):  
Nathalie E. Blachere ◽  
Zihai Li ◽  
Rajiv Y. Chandawarkar ◽  
Ryuichiro Suto ◽  
Navdeep S. Jaikaria ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
T Lymphocyte ◽  
Synthetic Peptides ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Response ◽  
Lymphocyte Response ◽  
Peptide Complexes

Heat shock protein (HSP) preparations derived from cancer cells and virus-infected cells have been shown previously to elicit cancer-specific or virus-specific immunity. The immunogenicity of HSP preparations has been attributed to peptides associated with the HSPs. The studies reported here demonstrate that immunogenic HSP–peptide complexes can also be reconstituted in vitro. The studies show that (a) complexes of hsp70 or gp96 HSP molecules with a variety of synthetic peptides can be generated in vitro; (b) the binding of HSPs with peptides is specific in that a number of other proteins tested do not bind synthetic peptides under the conditions in which gp96 molecules do; (c) HSP–peptide complexes reconstituted in vitro are immunologically active, as tested by their ability to elicit antitumor immunity and specific CD8+ cytolytic T lymphocyte response; and (d) synthetic peptides reconstituted in vitro with gp96 are capable of being taken up and re-presented by macrophage in the same manner as gp96– peptides complexes generated in vivo. These observations demonstrate that HSPs are CD8+ T cell response–eliciting adjuvants.

scholarly journals Analysis of complex formation of human recombinant hsp70 with tumor-associated peptides

2012 ◽  
Vol 58 (6) ◽  
pp. 651-661 ◽  
Author(s):  
V.A. Chernikov ◽  
N.V. Gorokhovets ◽  
L.V. Savvateeva ◽  
S.E. Severin
Keyword(s):  
Complex Formation ◽  
Antigenic Peptides ◽  
Cross Presentation ◽  
Hsp70 Family ◽  
Recombinant Hsp70 ◽  
Formation Method ◽  
Peptide Complexes ◽  
Antigen Presenting

Molecular chaperones of HSP70 family assists presentation of exogenous antigenic peptides by antigen-presenting cells (APC). HSP70-peptide complexes are powerful immunotherapeutic agents, which enhance cross-presentation of captured antigen in dendritic cells and macrophages. Several clinical trials have shown that HSP-based cancer vaccines possess good efficacy and safety. However, sometime it is impossible to isolate sufficient amount of vaccine. These make us to pay attention for recombinant HSP70-based vaccines and to optimize in vitro complex formation mechanism. Here we have investigated two human recombinant proteins HSP70HYB and HSC70. Optimal values of ADP concentration, pH, temperature and peptides excess are determined in this work. We have also shown that proposed complex formation method enriches eluted from HSP70-complexes peptide repertoire compared to in vivo assembled ones.

Studies on Avian Mucopolysaccharide–Peptide Complexes and on In Vivo Incorporation of D-[1-14C]hexosamine

1973 ◽  
Vol 51 (5) ◽  
pp. 642-653 ◽  
Author(s):  
John C. Hilborn ◽  
Phoebus A. Anastassiadis
Keyword(s):  
Molecular Weight ◽  
Amino Acid ◽  
Low Molecular Weight ◽  
White Leghorn ◽  
Peptide Complexes

The mucopolysaccharide–peptide complexes from White Leghorn skin, comb, wattle, heart, liver, and testis were isolated and analyzed for constituent carbohydrate and amino acid units. Individual mucopolysaccharides in each tissue were characterized using several techniques. All tissues examined, except liver, contained at least two mucopolysaccharides, including a low molecular weight component. The low molecular weight component appeared to be the only substance isolated from liver. The incorporation of D-[1-14C]hexosamine into acetone-dried tissues and mucopolysaccharide–peptide complexes was investigated. Intravenously injected D-[1-14C]galactosamine accumulated in the liver to a much greater extent than D-[1-14C]glucosamine. In addition, evidence was provided which indicated that glucosamine was converted to nonhexosamine products. The increase of radioactivity associated with mucopolysaccharide–peptide complexes with increasing time coincided with a decrease in liver radioactivity.

scholarly journals Self-RNA–antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8

2009 ◽  
Vol 206 (9) ◽  
pp. 1983-1994 ◽  
Author(s):  
Dipyaman Ganguly ◽  
Georgios Chamilos ◽  
Roberto Lande ◽  
Josh Gregorio ◽  
Stephan Meller ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Inflammatory Responses ◽  
Skin Lesions ◽  
Psoriatic Skin ◽  
Cationic Antimicrobial Peptide ◽  
Tnf Α ◽  
Peptide Complexes ◽  
Human Dendritic Cells ◽  
Dying Cells

Dendritic cell (DC) responses to extracellular self-DNA and self-RNA are prevented by the endosomal seclusion of nucleic acid–recognizing Toll-like receptors (TLRs). In psoriasis, however, plasmacytoid DCs (pDCs) sense self-DNA that is transported to endosomal TLR9 upon forming a complex with the antimicrobial peptide LL37. Whether LL37 also interacts with extracellular self-RNA and how this may contribute to DC activation in psoriasis is not known. Here, we report that LL37 can bind self-RNA released by dying cells, protect it from extracellular degradation, and transport it into endosomal compartments of DCs. In pDC, self-RNA–LL37 complexes activate TLR7 and, like self-DNA–LL37 complexes, trigger the secretion of IFN-α without inducing maturation or the production of IL-6 and TNF-α. In contrast to self-DNA–LL37 complexes, self-RNA–LL37 complexes also trigger the activation of classical myeloid DCs (mDCs). This occurs through TLR8 and leads to the production of TNF-α and IL-6, and the differentiation of mDCs into mature DCs. We also found that self-RNA–LL37 complexes are present in psoriatic skin lesions and are associated with mature mDCs in vivo. Our results demonstrate that the cationic antimicrobial peptide LL37 converts self-RNA into a trigger of TLR7 and TLR8 in human DCs, and provide new insights into the mechanism that drives the auto-inflammatory responses in psoriasis.

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