Cell Surface Heparan Sulfate Proteoglycans Influence MHC Class II-Restricted Antigen Presentation

Léonetti, Marc; Gadzinski, Adeline; Moine, G.

doi:10.4049/jimmunol.0902724

Cited by 16 publications

(15 citation statements)

References 41 publications

(40 reference statements)

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“…As we previously observed that a hybrid protein containing an HS-binding domain is more effectively captured by APCs and thus stimulates Th cells more efficiently (14), we decided to assess whether a similar behavior is observed for a wild-type protein intrinsically endowed with HS-binding ability. The observation that DT and CRM197 contain four clusters of basic residues prompted us to postulate that these proteins may both be able to bind HS.…”

Section: Discussionmentioning

confidence: 99%

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Acidosis Increases MHC Class II–Restricted Presentation of a Protein Endowed with a pH-Dependent Heparan Sulfate–Binding Ability

Knittel

Savatier

Upert

et al. 2015

The Journal of Immunology

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Heparan sulfate proteoglycans (HSPGs) are ubiquitously expressed molecules that participate in numerous biological processes. We previously showed that HSPGs expressed on the surface of APCs can serve as receptors for a hybrid protein containing an HS ligand and an Ag, which leads to more efficient stimulation of Th cells. To investigate whether such behavior is shared by proteins with inherent HS-binding ability, we looked for proteins endowed with this characteristic. We found that diphtheria toxin and its nontoxic mutant, called CRM197, can interact with HS. However, we observed that their binding ability is higher at pH 6 than at pH 7.4. Therefore, as extracellular acidosis occurs during infection by various micro-organisms, we assessed whether HS-binding capacity affects MHC class II–restricted presentation at different pHs. We first observed that pH decrease allows CRM197 binding to HSPG-expressing cells, including APCs. Then, we showed that this interaction enhances Ag uptake and presentation to Th cells. Lastly, we observed that pH decrease does not affect processing and presentation abilities of the APCs. Our findings show that acidic pH causes an HSPG-mediated uptake and an enhancement of T cell stimulation of Ags with the inherent ability to bind HSPGs pH-dependently. Furthermore, they suggest that proteins from micro-organisms with this binding characteristic might be supported more efficiently by the adaptive immune system when acidosis is triggered during infection.

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Section: Discussionmentioning

confidence: 99%

“…Indeed, we recently showed that an Ag previously coupled to an HSPG ligand can interact with HSPGs expressed on the surface of APCs. These molecules can then act either as receptors or as coreceptors and thus allow an increase in MHC class II-restricted presentation (14).…”

mentioning

confidence: 99%

Acidosis Increases MHC Class II–Restricted Presentation of a Protein Endowed with a pH-Dependent Heparan Sulfate–Binding Ability

Knittel

Savatier

Upert

et al. 2015

The Journal of Immunology

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“…Strong candidates are HSPGs, which are involved in the endocytosis of 3D8 scFv by HeLa cells (13) and in the endocytosis of CPPs, which contain multiple cationic amino acid residues similar to 3D8 scFv (36). It is reported that clustering of HSPGs triggers cytoskeletal remodeling and internalization pathways, and that HSPGs promote MHC class II-restricted Ag presentation by acting as coreceptors during Fcg-RII-mediated Ag presentation (37,38). However, in the current study, endocytosis of 3D8 scFv was not affected by treatment with heparinase III (which cleaves heparan sulfate of HSPGs; data not shown), despite the inhibition of 3D8 scFv endocytosis in the presence of heparin, a competitor of HSPGs.…”

Section: Discussionmentioning

confidence: 99%

An Anti-Nucleic Acid Antibody Delivers Antigen to the Cross-Presentation Pathway in Dendritic Cells and Potentiates Therapeutic Antitumor Effects

Pham

Woo

Kim

et al. 2012

The Journal of Immunology

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Cross-presentation is important for initiating CTL responses against tumors. Delivery of exogenous Ags to the cross-presentation pathway in dendritic cells (DCs), using a number of different carriers, has been attempted to further understand the mechanisms underlying cross-presentation and to develop therapeutic tumor vaccines. The present study reports a new antigenic carrier molecule: a single-chain V region fragment (scFv) of a nucleic acid–hydrolyzing Ab, 3D8. A fusion protein comprising 3D8 scFv and the CTL epitope OVA250–264 (chicken OVA aa 250–264) was internalized by DC2.4 DCs and processed via a proteasome-dependent, brefeldin- and cycloheximide-sensitive, chloroquine- and primaquine-insensitive pathway, resulting in loading of the CTL epitope onto H-2Kb. In vivo cross-presentation and cross-priming were efficient, even without adjuvant; injection of mice with 3D8 scFv-OVA250–264 induced cross-presentation of the CTL epitope by draining lymph node CD11c+ B7.1+ MHC class IIhigh DCs, elicited a CTL response, and suppressed the growth of tumors expressing the OVA epitope. This report shows that an anti-nucleic acid Ab is used to deliver exogenous Ag to the cross-presentation pathway and inhibit in vivo tumor growth.

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“…Besides being rapidly internalised via endocytosis (Tyagi et al, 2001), heparan sulphate is probably also involved in the initial binding step before internalisation (Ferrari et al, 2003). It can also act as a coreceptor for endocytosis (Leonetti et al, 2010). Interestingly, other glycosaminoglycans such as chondroitin sulphate and dermatan sulphate have been ruled out in the binding/internalisation of full length tat 1-86 (Tyagi et al, 2001) and tat 37-57 (Leonetti et al, 2010), but not for the shorter tat 48-60 (Sandgren et al, 2002).…”

Section: Tatmentioning

confidence: 99%

“…It can also act as a coreceptor for endocytosis (Leonetti et al, 2010). Interestingly, other glycosaminoglycans such as chondroitin sulphate and dermatan sulphate have been ruled out in the binding/internalisation of full length tat 1-86 (Tyagi et al, 2001) and tat 37-57 (Leonetti et al, 2010), but not for the shorter tat 48-60 (Sandgren et al, 2002). Classical endocytosis is an energy-and ATP-dependent mechanism.…”

Section: Tatmentioning

confidence: 99%

Peptides as Promising Non-Viral Vectors for Gene Therapy

Seow¹,

George²

2011

Non-Viral Gene Therapy

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Cell Surface Heparan Sulfate Proteoglycans Influence MHC Class II-Restricted Antigen Presentation

Abstract: Material

Cited by 16 publications

References 41 publications

Acidosis Increases MHC Class II–Restricted Presentation of a Protein Endowed with a pH-Dependent Heparan Sulfate–Binding Ability

Acidosis Increases MHC Class II–Restricted Presentation of a Protein Endowed with a pH-Dependent Heparan Sulfate–Binding Ability

An Anti-Nucleic Acid Antibody Delivers Antigen to the Cross-Presentation Pathway in Dendritic Cells and Potentiates Therapeutic Antitumor Effects

Peptides as Promising Non-Viral Vectors for Gene Therapy

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