Hyaluronic Acid Graft Polymers Displaying Peptide Antigen Modulate Dendritic Cell Response in Vitro

被引：14

作者：

Chittasupho, Chuda ^{[1
]}

Sestak, Joshua ^{[2
]}

Shannon, Laura ^{[3
]}

Siahaan, Teruna J. ^{[2
]}

Vines, Charlotte M. ^{[3
]}

Berkland, Cory ^{[2
,4
]}

机构：

[1] Srinakharinwirot Univ, Fac Pharm, Dept Pharmaceut Technol, Ongkharak 26120, Nakhonnayok, Thailand

[2] Univ Kansas, Dept Pharmaceut Chem, Lawrence, KS 66047 USA

[3] Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, Kansas City, KS 66160 USA

[4] Univ Kansas, Dept Chem & Petr Engn, Lawrence, KS 66045 USA

来源：

MOLECULAR PHARMACEUTICS | 2014年 / 11卷 / 01期

关键词：

peptides; hyaluronic acid; targeted delivery; dendritic cells; T cells; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; T-CELLS; MOLECULES; DISEASES; AMINOOXY; BINDING; LFA-1; SUPPRESSION; ACTIVATION; INHIBITOR;

D O I：

10.1021/mp4003909

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

A novel oxime grafting scheme was utilized to conjugate an ICAM-1 ligand (LABL), a cellular antigen ovalbumin (OVA), or both peptides simultaneously to hyaluronic acid (HA). Samples of HA only and the various peptide grafted HA were found to bind to dendritic cells (DCs). HA with grafted LABL and OVA showed the greatest binding to DCs. Dendritic cells treated with HA, HA with grafted LABL, or HA with grafted LABL and OVA significantly suppressed T cell and DC conjugate formation and T cell proliferation and reduced proinflammatory cytokine production compared to untreated cells. These results suggest that HA serves as an effective backbone for multivalent ligand presentation for inhibiting T cell response to antigen presentation. In addition, multivalent display of both antigen and an ICAM-1 inhibitor (LABL) may enhance binding to DCs and could potentially disrupt cellular signaling leading to auto-immunity.

引用

页码：367 / 373

页数：7

共 24 条

[1]

Babbitt BP, 2005, J IMMUNOL, V175, P4163

[2] ANTIGENIC-COMPETITION AT THE LEVEL OF PEPTIDE-IA BINDING [J].

BABBITT, BP ;

MATSUEDA, G ;

HABER, E ;

UNANUE, ER ;

ALLEN, PM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (12) :4509-4513

[3] Distinct roles for LFA-1 and CD28 during activation of naive T cells: Adhesion versus costimulation [J].

Bachmann, MF ;

McKallFaienza, K ;

Schmits, R ;

Bouchard, D ;

Beach, J ;

Speiser, DE ;

Mak, TW ;

Ohashi, PS .

IMMUNITY, 1997, 7 (04) :549-557

[4] Dendritic cells and cytokines in human inflammatory and autoimmune diseases [J].

Blanco, Patrick ;

Palucka, A. Karolina ;

Pascual, Virginia ;

Banchereau, Jacques .

CYTOKINE & GROWTH FACTOR REVIEWS, 2008, 19 (01) :41-52

[5] Synthesis of Aminooxy and N-Alkylaminooxy Amines for Use in Bioconjugation [J].

Carrasco, Michael R. ;

Alvarado, Carolina I. ;

Dashner, Scott T. ;

Wong, Amanda J. ;

Wong, Michael A. .

JOURNAL OF ORGANIC CHEMISTRY, 2010, 75 (16) :5757-5759

[6] Immunologic messenger molecules: Cytokines, interferons, and chemokines [J].

Commins, Scott P. ;

Borish, Larry ;

Steinke, John W. .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2010, 125 (02) :S53-S72

[7] Characterization and quantitation of peptide-MHC complexes produced from hen egg lysozyme using a monoclonal antibody [J].

Dadaglio, G ;

Nelson, CA ;

Deck, MB ;

Petzold, SJ ;

Unanue, ER .

IMMUNITY, 1997, 6 (06) :727-738

[8] ANTIGEN ANALOG MAJOR HISTOCOMPATIBILITY COMPLEXES ACT AS ANTAGONISTS OF THE T-CELL RECEPTOR [J].

DEMAGISTRIS, MT ;

ALEXANDER, J ;

COGGESHALL, M ;

ALTMAN, A ;

GAETA, FCA ;

GREY, HM ;

SETTE, A .

CELL, 1992, 68 (04) :625-634

[9]

Haegel-Kronenberger H, 1998, J IMMUNOL, V161, P3902

[10] Antigen-specific suppression of experimental autoimmune encephalomyelitis by a novel bifunctional peptide inhibitor [J].

Kobayashi, Naoki ;

Kobayashi, Hitomi ;

Gu, Leo ;

Malefyt, Thomas ;

Siahaan, Teruna J. .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2007, 322 (02) :879-886

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