Mannose Receptor Mediated Uptake of Antigens Strongly Enhances HLA-Class II Restricted Antigen Presentation by Cultured Dendritic Cells

Mc, Tan; Am, Mommaas; Drijfhout, Jan W.; Jordens, Reina; Jj, Onderwater; Verwoerd, Desirée; Aa, Mulder; An, van der Heiden; Th, Ottenhoff; Cella, Marina; Tulp, A.; Neefjes, Jacques; Koning, Frits

doi:10.1007/978-1-4757-9966-8_28

Cited by 118 publications

(138 citation statements)

References 12 publications

Supporting

Mentioning

131

Contrasting

Unclassified

Order By: Relevance

“…3E), suggesting the presence of divergent routing mechanisms. While mannose-binding receptors such as DC-SIGN and MR mediate MDO delivery and processing in acidic lysosomes, resulting in MHC class II presentation [4,8], there is an unknown routing mechanism targeting MHC class I-loading compartments, leading to cross-presentation. It is tempting to postulate a role of dendrimer in this process, since it contributes significantly to MDO binding to DC.…”

Section: Discussionmentioning

confidence: 99%

“…Uptake of antigens via these receptors on the APC surface is followed by delivery into the endolysosomal pathway, leading to MHC-class II presentation [4]. In comparison to antigens internalized via the fluid phase (e.g., pinocytosis), this pathway of antigen uptake in DC results in a considerable increase of efficiency in antigen presentation and T cell stimulation [5][6][7][8]. For instance, it was shown that antigen uptake mediated by mannosebinding receptors increased antigen presentation to T cells up to 100-fold [5].…”

Section: Introductionmentioning

confidence: 99%

“…For instance, it was shown that antigen uptake mediated by mannosebinding receptors increased antigen presentation to T cells up to 100-fold [5]. Mannosylated antigens were efficiently internalized by DC and localized in the MHC class II-specific compartments and lysosomes, resulting in 200-10 000-fold enhanced potency in stimulating specific MHC class II-restricted T cells [8]. Yeast-derived recombinant OVA antigens that contained branched N-and O-linked mannose were far more immunogenic than non-mannosylated OVA [6].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Delivery of antigen using a novel mannosylated dendrimer potentiates immunogenicity in vitro and in vivo

et al. 2008

View full text Add to dashboard Cite

Antigen mannosylation has been shown to be an effective approach to potentiate antigen immunogenicity, due to the enhanced antigen uptake and presentation by APC. To overcome disadvantages associated with conventional methods used to mannosylate antigens, we have developed a novel mannose-based antigen delivery system that utilizes a polyamidoamine (PAMAM) dendrimer. It is demonstrated that mannosylated dendrimer ovalbumin (MDO) is a potent immune inducer. With a strong binding avidity to DC, MDO potently induced OVA-specific T cell response in vitro. It was found that the immunogenicity of MDO was due not only to enhanced antigen presentation, but also to induction of DC maturation. Mice immunized with MDO generated strong OVA-specific CD4 + /CD8 + T cell and antibody responses. MDO also targeted lymph node DC to crosspresent OVA, leading to OTI CD8 + T cell proliferation. Moreover, upon challenge with B16-OVA tumor cells, tumors in mice pre-immunized with MDO either did not grow or displayed a much more delayed onset, and had slower kinetics of growth than those of OVA-immunized mice. This mannose-based antigen delivery system was applied here for the first time to the immunization study. With several advantages and exceptional adjuvanticity, we propose mannosylated dendrimer as a potential vaccine carrier.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Delivery of antigen using a novel mannosylated dendrimer potentiates immunogenicity in vitro and in vivo

et al. 2008

View full text Add to dashboard Cite

show abstract

“…This 205-kD protein contains C-type lectin domains and is a homologue to the MR CD206. In fact, both the MR [47,48] and DEC-205 [49,50] mediate antigen uptake. CD205 expression on human DC is up-regulated upon maturation, and this endocytic receptor is involved in both antigen uptake and processing.…”

Section: Discussionmentioning

confidence: 99%

C‐reactive protein impairs human CD14⁺ monocyte‐derived dendritic cell differentiation, maturation and function

Zhang¹,

Becnel

Li³

et al. 2006

Eur J Immunol

View full text Add to dashboard Cite

C-reactive protein (CRP) is an acute phase reactant protein considered to be the prototypic marker for inflammation and its associated diseases. However, little is known about how CRP affects the immune system. In this study, we investigated the effect of CRP on dendritic cell (DC) differentiation, activation and biological functions. CD14 + monocytes were purified from PBMC and differentiated into DC in vitro. CRP (10 lg/ mL) substantially down-regulated expression of DC-SIGN (CD209) and the costimulatory molecules CD40 and CD86 during DC differentiation. This inhibitory effect was more pronounced when CRP was added at the early stage (0-2 days) of DC differentiation. The inhibitory effect of CRP could be specifically blocked by an anti-CD32 Ab. In addition, CRP dramatically down-regulated expression of the antigenuptake molecules CD205 and CD206, resulting in reduced DC endocytosis. Furthermore, CRP down-regulated expression of the costimulatory molecules CD40, CD80 and CD86 as well as the DC maturation marker CD83 after lipopolysaccharideinduced DC maturation. CRP-treated DC also showed an inhibitory effect on allogeneic T cell proliferation in a mixed leukocyte reaction. CRP treatment of activated DC preferentially decreased production of the proinflammatory and inflammatory cytokines IL-6, IL-8, IL-12, TNF-a, MIP-1a, MIP-1b and MCP-1. This work reveals a new role for CRP in modulating the immune system by inhibiting DC differentiation, maturation and functions mainly through FccRIIa/CD32.

show abstract

“…Ligands containing mannan or mannose have been successfully used in various forms to direct antigens to APCs, thus generating more efficient immune responses (Tan et al, 1997;Agnes et al, 1998;Apostolopoulos et al, 2000;Keler et al, 2004). The use of MR ligands for targeting APCs has been widely applied for enhancing antigen-specific immunity, but these ligands are not specific for MR, thus the contribution of MR relative to other mannan-binding receptors, such as DC-specific intracellular adhesion molecule (ICAM)-grabbing non-integrin (DC-SIGN), to the enhanced immune responses remains to be established.…”

Section: Targeting Antigens To Clrsmentioning

confidence: 99%

Antibody-targeted vaccines

Keler

Ramakrishna

et al. 2007

Oncogene

View full text Add to dashboard Cite

Mannose Receptor Mediated Uptake of Antigens Strongly Enhances HLA-Class II Restricted Antigen Presentation by Cultured Dendritic Cells

Cited by 118 publications

References 12 publications

Delivery of antigen using a novel mannosylated dendrimer potentiates immunogenicity in vitro and in vivo

Delivery of antigen using a novel mannosylated dendrimer potentiates immunogenicity in vitro and in vivo

C‐reactive protein impairs human CD14⁺ monocyte‐derived dendritic cell differentiation, maturation and function

Antibody-targeted vaccines

Contact Info

Product

Resources

About

Mannose Receptor Mediated Uptake of Antigens Strongly Enhances HLA-Class II Restricted Antigen Presentation by Cultured Dendritic Cells

Cited by 118 publications

References 12 publications

Delivery of antigen using a novel mannosylated dendrimer potentiates immunogenicity in vitro and in vivo

Delivery of antigen using a novel mannosylated dendrimer potentiates immunogenicity in vitro and in vivo

C‐reactive protein impairs human CD14+ monocyte‐derived dendritic cell differentiation, maturation and function

Antibody-targeted vaccines

Contact Info

Product

Resources

About

C‐reactive protein impairs human CD14⁺ monocyte‐derived dendritic cell differentiation, maturation and function