Linear and cyclic LFA-1 and ICAM-1 peptides inhibit T cell adhesion and function

Tibbetts, Scott A.; Jois, D. S. Seetharama; Siahaan, Teruna J.; Benedict, Stephen H.; Chan, Marcia A.

doi:10.1016/s0196-9781(00)00255-2

Cited by 50 publications

(70 citation statements)

References 21 publications

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“…Previously, we have discovered that linear and cyclic peptides derived from the α-and β-subunits of LFA-1 can inhibit homotypic and heterotypic T-cell adhesion as well as mixed lymphocyte reaction (MLR) [15,16]. The α-subunit peptides were derived from the I-domain [17,18] and the divalent cation-binding region of LFA-1 [18,19].…”

Section: Introductionmentioning

confidence: 99%

“…Peptides derived from the divalent cation-binding region of the α-subunit were found to inhibit homotypic T-cell adhesion and could complex with calcium and magnesium ions as in the LFA-1 receptor [19]. Finally, β 2 -subunit-derived peptides can bind to ICAM-1 and inhibit homotypic T-cell adhesion and suppress MLR [15,16]. Interestingly, a β-subunit peptide, LBE, was found to enhance the binding of cLABL peptide to ICAM-1 [20].…”

Section: Introductionmentioning

confidence: 99%

“…We also discovered linear and cyclic peptides derived from ICAM-1 that can inhibit ICAM-1/LFA-1-mediated T-cell adhesion [15,16,18]. Linear peptides (ICAM 1-21 and ICAM ) derived from the D1-domain of ICAM-1 were found to inhibit homotypic T-cell adhesion and mixed lymphocyte reaction (MLR) [15].…”

Section: Introductionmentioning

confidence: 99%

“…20, (2003 [12][13][14][15][16][17][18][19][20][21] ). The cyclic peptides were also able to inhibit homotypic and heterotypic T-cell adhesion, presumably by binding to the α-subunit of LFA-1 [16]. However, the detailed mechanisms of binding of these peptides to LFA-1 on the surface of T-cells are not well characterized.…”

Section: Introductionmentioning

confidence: 99%

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Anderson

Siahaan

2003

Pharmaceutical Research

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Abstract:Purpose Peptides derived from the Domain 1 of the adhesion molecule ICAM-1 are being developed as targeting ligands for LFA-1 receptors expressed on activated T-cells. This work aims to elucidate the binding and internalization of ICAM-1-derived cyclic peptides (cIBL, cIBC, and cIBR) to LFA-1.Methods 96-well plates coated with soluble LFA-1 (sLFA-1) were used to characterize the binding of FITC-labeled peptide. An anti-CD11a antibody to the I-domain of LFA-1 was used to inhibit the binding of these peptides, which was quantified using a fluorescence plate reader. An unrelated FITC-labeled cyclic peptide was used as a negative control and PE-labeled antiCD11a antibodies (PE-R3.2 and PE-R7.1) were used as positive controls. Peptide binding to cell surface LFA-1 was visualized using co-localization of FITC-cIBR peptide and PE-labeled anti-CD18 antibody (LFA-1 β-subunit) on SKW-3 T-cells by fluorescent microscopy. Inhibition of ICAM-1-binding to LFA-1 by peptides was evaluated using a Biacore assay. Binding and internalization of FITC-labeled peptides was evaluated by flow cytometry and confocal microscopy at 4 and 37ºC.Results These FITC-labeled cyclic peptides bind to sLFA-1 and can be blocked by an anti-CD11a antibody to the I-domain, suggesting that their binding site is on the I-domain of LFA-1. The FITC-cIBR peptide was localized with an anti-CD18 antibody on the surface of T-cells, indicating that the FITC-cIBR peptide binds to LFA-1 on the cell surface. Flow cytometry and confocal microscopy demonstrated that FITC-labeled peptides were internalized in temperature dependent manner. Biacore analysis, demonstrated these peptides did not inhibit sICAM-1 from binding to immobilized sLFA-1. However, the binding properties of the soluble forms of LFA-1 and ICAM-1 may not correlate to their interaction at the cell surface.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anderson

Siahaan

2003

Pharmaceutical Research

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“…Fuzeon, inhibitor of HIV-1 cell entry) (3,4). However, the functional activity of many short peptides is usually substantially lower (50 -200-fold) than that of their parental proteins (5)(6)(7)(8)(9). In general, this is due to their diminished solubility, stability, and/or enhanced propensity for aggregation (5)(6)(7)(8)(9)(10)(11).…”

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confidence: 99%

Chimeric Glutathione S-Transferases Containing Inserts of Kininogen Peptides

Bentley

Merkulov

Peng

et al. 2012

Journal of Biological Chemistry

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Background: Short human kininogen (HK) peptides can be used as therapeutic agents. Results: The biological activity of the HK peptides is dramatically enhanced following insertion into GST. Conclusion: The efficacy of short peptides can be enhanced by insertion into GST without affecting GST structure. Significance: Intra-backbone insertions of small peptides into easily expressed, well characterized soluble proteins may help to create novel protein therapeutics.

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