Red-cell ICAM-4 is a ligand for the monocyte/macrophage integrin CD11c/CD18: characterization of the binding sites on ICAM-4

Ihanus, Eveliina; Uotila, Liisa M.; Toivanen, Anne; Varis, Minna; Gahmberg, Carl G.

doi:10.1182/blood-2006-04-014878

Cited by 88 publications

(79 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Peptides: p17 (LNCSNCPQPQNSSLRTPLRQG-GS AGSAGSAG-HHHHHHHHHHHH) and p18 (SLERFTGL DLANVTLTYEFAAGPRDFWQP-GSAGSAGSAG-HHHHHH HHHHHH) contained amino acids 37-58 and 149-177, respectively, of human ICAM-4; and peptide p30 (HHHHHHHHH HHH-GSGSGSGS-CGRWSGWPADLC) contained a sequence identified by phage display to bind CD11c/CD18. 21,22 The peptide 12His was used as control since it reduces nonspecific binding of Ni-NTA 3 -DTDA-liposomes to cells. All peptides were synthesized (p17 and p30 also were cyclized) and HPLC-purified by the BioMolecular Resource Facility, JCSMR (ANU); stock solutions were prepared in distilled water, and stored at À20 C.…”

Section: Peptidesmentioning

confidence: 99%

“…Synthetic peptides of sequence related to two regions of human ICAM-4 reported to bind to CD11c/CD18, 21 and a sequence identified by phage display to bind to CD11c/CD18, 22 were incorporated into peptides p17, p18 and p30, that contain a His-tag to enable their anchoring onto NTA 3 -DTDA-liposomes for use as Ag-targeting moieties. Both ICAM-4-related peptides were designed to have the His-tag at the C-terminal to better mimic the orientation (when anchored onto NTA 3 -DTDA-liposomes) of the corresponding regions of ICAM-4 predicted to interact with CD11c/CD18 in a 3-D model of the ICAM-4-CD11c/ CD18 interaction.…”

Section: Design Of Peptides For Targeting Liposomes To Cd11cmentioning

confidence: 99%

mentioning

confidence: 99%

“…18,19 Among the purported ligands for CD11c/CD18 are ICAM-1 (Intra cellular adhesion molecule)-1 and ICAM-4. 20,21 Interestingly, the regions of ICAM-4 involved in the interaction with CD11c/CD18 have been defined, and two synthetic peptides of sequence related to that found in ICAM-4 were found to bind selectively to soluble CD11c/CD18. 21 Phage display also has identified peptides that purportedly interact with CD11c/CD18.…”

mentioning

confidence: 99%

“…20,21 Interestingly, the regions of ICAM-4 involved in the interaction with CD11c/CD18 have been defined, and two synthetic peptides of sequence related to that found in ICAM-4 were found to bind selectively to soluble CD11c/CD18. 21 Phage display also has identified peptides that purportedly interact with CD11c/CD18. 22 In previous studies we showed that, the chelator lipid 3(nitrilotriacetic acid)-ditetradecyl-amine (NTA 3 -DTDA) can be incorporated into liposomes and membrane vesicles to enable engraftment of His-tagged ScFv targeting CD11c on DCs.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Ag‐bearing liposomes engrafted with peptides that interact with CD11c/CD18 induce potent Ag‐specific and antitumor immunity

Faham

Altin

2011

Intl Journal of Cancer

View full text Add to dashboard Cite

Dendritic cells (DCs) play key role in eliciting antigen (Ag)-specific immune responses, and crucial to this is the uptake of Ag via surface receptors including the heterodimeric integrin CD11c/CD18. Here we report that CD11c/CD18-interacting peptides can be used as targeting moieties to deliver liposomal Ag to antigen presenting cells (APCs) and elicit Ag-specific and antitumor immunity. Two peptides of sequence related to human ICAM-4 and previously reported to bind CD11c/CD18, and a 12-mer cyclic peptide previously identified by phage display to bind CD11c/CD18, were produced synthetically, and tested for their ability to target liposomal Ag. The three peptides were designed to contain a shorter spacer to reduce steric hindrance, and a His-tag to enable engraftment onto liposomes incorporated with chelator lipid. Our results show that the three peptides, denoted as p17, p18 and p30, promote strong binding of liposomes to CD11c 1 and CD11b 1 cells in vitro and in vivo. Vaccination of mice with Ag-bearing liposomes engrafted with the peptides, particularly p18 and p30, induced Agspecific T cell priming and antibody production. Importantly, the vaccination of C57BL/6 mice with syngeneic B16-OVA-derived plasma membrane vesicles (PMVs) engrafted with p18 and p30 peptide showed dramatic antitumor responses, inhibiting tumor growth/metastasis in both the lung and subcutaneous tumor models, with a high proportion of the mice apparently being ''cured'' of their tumors. The engraftment of p18 and p30 peptides onto liposomes and PMVs, thus provides an effective means to target Ags to DCs in vivo, for the development of effective cancer vaccines and immunotherapies.The use of antigen-pulsed dendritic cells (DCs) has shown promise for developing cell-based cancer vaccines and immunotherapies. 1 DCs play a key role in eliciting Ag-specific immune responses, and crucial to this is the uptake of antigen (Ag) via a number of DC surface receptors such as Fc-receptors, C-type lectins, Toll-like receptors (TLRs) and integrin receptor CD11c/CD18. [2][3][4][5][6] The unique ability of DCs to prime naïve T cells makes them ideal targets for Ag-delivery and vaccine development. 7 To better exploit this potential, techniques have been used to target protein-Ag to DCs in vivo, potentially circumventing the need to manipulate DCs ex vivo for cancer immunotherapy. 8,9 Typical strategies involve conjugation of Ag to mAbs, ScFv or Fab fragments specific for a DC surface marker or Ag-uptake receptor. 4,6,10,11 To facilitate the delivery of multiple Ags simultaneously, we previously attached recombinant co-stimulatory molecules and ScFv to Ag-containing delivery vehicles such as liposomes and membrane vesicles. 8,12 The vaccination of mice with such constructs can elicit potent immune responses and inhibit tumor growth in tumor models. 12 However, mAbs, ScFvs, and recombinant proteins for use as DC-targeted conjugates, or as targeting moieties for liposomes, can be time-consuming and expensive to produce for clinical applications.The use of...

show abstract

Section: Peptidesmentioning

confidence: 99%

Section: Design Of Peptides For Targeting Liposomes To Cd11cmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations