scholarly journals Targeted Delivery of Antigen Processing Inhibitors to Antigen Presenting Cells via Mannose Receptors

2010 ◽  
Vol 5 (5) ◽  
pp. 461-476 ◽  
Author(s):  
Eun-Ang Raiber ◽  
Calogero Tulone ◽  
Yanjing Zhang ◽  
Luisa Martinez-Pomares ◽  
Emily Steed ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Antigen Processing ◽  
Antigen Presenting Cells ◽  
Antigen Presenting ◽  
Mannose Receptors

scholarly journals Enhancing Protective Efficacy of Poultry Vaccines through Targeted Delivery of Antigens to Antigen-Presenting Cells

Vaccines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 75 ◽  
Author(s):  
Angita Shrestha ◽  
Jean-Remy Sadeyen ◽  
Munir Iqbal
Keyword(s):  
B Cells ◽  
Avian Influenza ◽  
Targeted Delivery ◽  
Vaccine Development ◽  
Antigen Presenting Cells ◽  
Influenza Viruses ◽  
Effective Vaccine ◽  
Capture Process ◽  
Selective Delivery ◽  
Antigen Presenting

Avian viral diseases including avian influenza, Marek’s disease and Newcastle disease are detrimental to economies around the world that depend on the poultry trade. A significant zoonotic threat is also posed by avian influenza viruses. Vaccination is an important and widely used method for controlling these poultry diseases. However, the current vaccines do not provide full protection or sterile immunity. Hence, there is a need to develop improved vaccines. The major aim of developing improved vaccines is to induce strong and specific humoral and cellular immunity in vaccinated animals. One strategy used to enhance the immunogenicity of vaccines is the selective delivery of protective antigens to antigen-presenting cells (APCs) including dendritic cells, macrophages and B cells. APCs have a central role in the initiation and maintenance of immune responses through their ability to capture, process and present antigens to T and B cells. Vaccine technology that selectively targets APCs has been achieved by coupling antigens to monoclonal antibodies or ligands that are targeted by APCs. The aim of this review is to discuss existing strategies of selective delivery of antigens to APCs for effective vaccine development in poultry.

scholarly journals The Majority of H2-M3 Is Retained Intracellularly in a Peptide-Receptive State and Traffics to the Cell Surface in the Presence of N-Formylated Peptides

1999 ◽  
Vol 190 (3) ◽  
pp. 423-434 ◽  
Author(s):  
Nancy M. Chiu ◽  
Taehoon Chun ◽  
Miriam Fay ◽  
Manas Mandal ◽  
Chyung-Ru Wang
Keyword(s):  
Cell Surface ◽  
Antigen Processing ◽  
Cytotoxic T Cells ◽  
Antigen Presenting Cells ◽  
Cell Types ◽  
Surface Expression ◽  
Peptide Vaccination ◽  
Histocompatibility Complex ◽  
Antigen Presenting ◽  
Class Ib

We used a new monoclonal antibody (mAb 130) to analyze the intracellular trafficking and surface expression of H2-M3, the major histocompatibility complex class Ib molecule that presents N-formylated peptides to cytotoxic T cells. M3 surface expression is undetectable in most cell types due to the paucity of endogenous antigen. M3 is induced on the cell surface by addition of high-affinity N-formylated peptides from mitochondria and listeria. Peptide-induced M3 expression is most efficient on antigen presenting cells. Basal and inducible expression of M3 is transporter associated with antigen processing (TAP)-dependent, distinguishing M3 from the class Ib molecules TL and CD1. Unlike the expression of class Ia molecules and a previously described M3/Ld chimera, surface expression of M3 cannot be rescued by lowered temperature, suggesting that the α3 domain and transmembrane region of M3 may control trafficking. Pulse–chase analysis and use of trafficking inhibitors revealed a pool of empty M3 in the endoplasmic reticulum or early Golgi apparatus. Addition of exogenous peptide allows maturation with kinetics matching those of Dd. The lack of endogenous N-formylated peptide allows discovery of novel pathogen-derived peptides in normal antigen presenting cells. The nonpolymorphic nature of M3 and its ability to present bacterial antigens rapidly and dominantly make it an attractive target for peptide vaccination strategies.

scholarly journals Enhanced binding of peptide antigen to purified class II major histocompatibility glycoproteins at acidic pH.

1991 ◽  
Vol 174 (5) ◽  
pp. 1111-1120 ◽  
Author(s):  
P E Jensen
Keyword(s):  
Electrostatic Interactions ◽  
Antigen Processing ◽  
Ph Dependence ◽  
Peptide Binding ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Hydrogen Ion Concentration ◽  
Peptide Antigens ◽  
Antigen Presenting

Helper T lymphocytes recognize peptide antigens stably associated with class II major histocompatibility complex (MHC) glycoproteins on the surface of antigen-presenting cells and serve to regulate a wide variety of immune responses. A previous study from our laboratory had demonstrated that the functional association of various peptide antigens with the antigen-presenting cell membrane was increased at pH 5 as compared to pH 7, consistent with the potential role of acidic endosomal compartments in antigen processing. The mechanism for this effect was not determined. In the present study, assays using purified class II glycoprotein were used to further define this mechanism. The potential requirement for pH-dependent interactions involving non-MHC membrane components was excluded in functional assays with purified class II reconstituted in artificial membranes containing only neutral phospholipids and cholesterol. The association of HEL(104-120) with I-Ed, and OVA(323-339) with I-Ad, was increased at pH 5, as measured by activation of specific T cell hybridomas. An enzyme immunoassay was developed to measure the binding of biotin-labeled peptides to purified class II in detergent micelles. The pH dependence of binding paralleled our previous functional results. Optimum binding of biotin-HEL(104-120) to I-Ed was observed at pH approximately 4.5, whereas maximum binding of biotin-Myo(106-118) to I-Ad occurred at pH approximately 5.5. The latter peptide also bound weakly to I-Ed, but with a pH dependence similar to that observed using HEL(104-120). Further experiments with biotin-HEL(104-120)/I-Ed indicated that both the apparent affinity and the apparent concentration of peptide-binding sites are increased as hydrogen ion concentration is increased from pH 7 to pH 5. The effect of pH in this range was largely reversible and was not associated with a change in peptide dissociation that could be measured with our assay system. Binding was not inhibited in the presence of 1.5 M NaCl, suggesting that electrostatic interactions between HEL(104-120) and I-Ed are not essential for binding. It is proposed that protonation of a critical group(s) in the class II molecule regulates its capacity to form stable complexes with peptide. However, this effect alone does not fully account for the rapid kinetics of peptide binding observed in experiments with intact antigen-presenting cells.

scholarly journals Intracellular Delivery of a Cytolytic T-Lymphocyte Epitope Peptide by Pertussis Toxin to Major Histocompatibility Complex Class I without Involvement of the Cytosolic Class I Antigen Processing Pathway

1999 ◽  
Vol 67 (2) ◽  
pp. 602-607 ◽  
Author(s):  
Nicholas H. Carbonetti ◽  
Teresa J. Irish ◽  
Carrie H. Chen ◽  
Colin B. O’Connell ◽  
Gregg A. Hadley ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
T Lymphocyte ◽  
Pertussis Toxin ◽  
Antigen Processing ◽  
Antigen Presenting Cells ◽  
Class I ◽  
Histocompatibility Complex ◽  
Cytolytic T Lymphocyte ◽  
Antigen Presenting

ABSTRACT A CD8+ cytolytic T-lymphocyte (CTL) response to antigen-presenting cells generally requires intracellular delivery or synthesis of antigens in order to access the major histocompatibility complex (MHC) class I processing and presentation pathway. To test the ability of pertussis toxin (PT) to deliver peptides to the class I pathway for CTL recognition, we constructed fusions of CTL epitope peptides with a genetically detoxified derivative of PT (PT9K/129G). Two sites on the A (S1) subunit of PT9K/129G tolerated the insertion of peptides, allowing efficient assembly and secretion of the holotoxin fusion by Bordetella pertussis. Target cells incubated with these fusion proteins were specifically lysed by CTLs in vitro, and this activity was shown to be MHC class I restricted. The activity was inhibited by brefeldin A, suggesting a dependence on intracellular trafficking events, but was not inhibited by the proteasome inhibitors lactacystin andN-acetyl-l-leucyl-l-leucyl-l-norleucinal (LLnL). Furthermore, the activity was present in mutant antigen-presenting cells lacking the transporter associated with antigen processing, which transports peptides from the cytosol to the endoplasmic reticulum for association with MHC class I molecules. PT may therefore bypass the proteasome-dependent cytosolic pathway for antigen presentation and deliver epitopes to class I molecules via an alternative route.

Determining the Fate of Glycopeptides During Antigen Processing in Antigen Presenting Cells

2001 ◽  
pp. 1041-1042
Author(s):  
Rodney Gagné ◽  
Shiro Komba ◽  
Teis Jensen ◽  
Monika Gad ◽  
Ole Werdelin ◽  
...  
Keyword(s):  
Antigen Processing ◽  
Antigen Presenting Cells ◽  
Antigen Presenting
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