Regulation of Human T Lymphocyte Coactivation with an α4 Integrin Antagonist Peptide

Bradley W. McIntyre, Darren G. Woodside, Denise A. Caruso, David K. Wooten, Scott I. Simon, Sriram Neelamegham, Joanna K. Revelle, Peter Vanderslice

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The cyclic hexapeptide CWLDVC (TBC 772) is an antagonist of α4 integrins and a potent inhibitor of lymphocyte interactions with fibronectin, vascular cell adhesion molecule-1, and muscosal vascular addressin cell adhesion molecule-1 (MAdCAM-1). As such, peptide TBC 772 effectively inhibits the activation of freshly isolated human T lymphocytes stimulated with purified vascular cell adhesion molecule-1 coimmobilized with anti-CD3 mAb. The influence of peptide binding on distinct sites of the α4β1 complex was determined by flow cytometry and cellular adhesion assays employing a panel of mAbs. Binding of the α4-specific mAb L25 and the β1-specific mAb 33B6 was not altered by the peptide; however, binding of mAb 19H8, which is specific for a combinatorial epitope of α4β1, was dramatically inhibited. Treatment of lymphocytes with the peptide caused an increase in a ligand-induced epitope on β1 integrin defined by mAb 15/7. In T cell activation studies using coimmobilized anti-CD3 mAb and the anti-integrin mAbs, the peptide had broader inhibitory activity, suppressing costimulation induced by all the integrin mAbs. The peptide was not generally toxic and was integrin selective in its suppressive activity, as coactivation by ligation of CD3 in conjunction with CD28 or CD26 was not affected. These results suggest that the antagonist peptide CWLDVC can effectively neutralize integrin coactivation systems by a mechanism independent of competitive binding.

Original languageEnglish (US)
Pages (from-to)4180-4186
Number of pages7
JournalJournal of Immunology
Volume158
Issue number9
StatePublished - May 1 1997
Externally publishedYes

Fingerprint

Integrins
T-Lymphocytes
Peptides
Vascular Cell Adhesion Molecule-1
Epitopes
Lymphocytes
Competitive Binding
Poisons
Fibronectins
Ligation
Flow Cytometry
Ligands

ASJC Scopus subject areas

  • Immunology

Cite this

McIntyre, B. W., Woodside, D. G., Caruso, D. A., Wooten, D. K., Simon, S. I., Neelamegham, S., ... Vanderslice, P. (1997). Regulation of Human T Lymphocyte Coactivation with an α4 Integrin Antagonist Peptide. Journal of Immunology, 158(9), 4180-4186.

Regulation of Human T Lymphocyte Coactivation with an α4 Integrin Antagonist Peptide. / McIntyre, Bradley W.; Woodside, Darren G.; Caruso, Denise A.; Wooten, David K.; Simon, Scott I.; Neelamegham, Sriram; Revelle, Joanna K.; Vanderslice, Peter.

In: Journal of Immunology, Vol. 158, No. 9, 01.05.1997, p. 4180-4186.

Research output: Contribution to journalArticle

McIntyre, BW, Woodside, DG, Caruso, DA, Wooten, DK, Simon, SI, Neelamegham, S, Revelle, JK & Vanderslice, P 1997, 'Regulation of Human T Lymphocyte Coactivation with an α4 Integrin Antagonist Peptide', Journal of Immunology, vol. 158, no. 9, pp. 4180-4186.
McIntyre BW, Woodside DG, Caruso DA, Wooten DK, Simon SI, Neelamegham S et al. Regulation of Human T Lymphocyte Coactivation with an α4 Integrin Antagonist Peptide. Journal of Immunology. 1997 May 1;158(9):4180-4186.
McIntyre, Bradley W. ; Woodside, Darren G. ; Caruso, Denise A. ; Wooten, David K. ; Simon, Scott I. ; Neelamegham, Sriram ; Revelle, Joanna K. ; Vanderslice, Peter. / Regulation of Human T Lymphocyte Coactivation with an α4 Integrin Antagonist Peptide. In: Journal of Immunology. 1997 ; Vol. 158, No. 9. pp. 4180-4186.
@article{884280175dde4c319a7b7aeb6daf60f1,
title = "Regulation of Human T Lymphocyte Coactivation with an α4 Integrin Antagonist Peptide",
abstract = "The cyclic hexapeptide CWLDVC (TBC 772) is an antagonist of α4 integrins and a potent inhibitor of lymphocyte interactions with fibronectin, vascular cell adhesion molecule-1, and muscosal vascular addressin cell adhesion molecule-1 (MAdCAM-1). As such, peptide TBC 772 effectively inhibits the activation of freshly isolated human T lymphocytes stimulated with purified vascular cell adhesion molecule-1 coimmobilized with anti-CD3 mAb. The influence of peptide binding on distinct sites of the α4β1 complex was determined by flow cytometry and cellular adhesion assays employing a panel of mAbs. Binding of the α4-specific mAb L25 and the β1-specific mAb 33B6 was not altered by the peptide; however, binding of mAb 19H8, which is specific for a combinatorial epitope of α4β1, was dramatically inhibited. Treatment of lymphocytes with the peptide caused an increase in a ligand-induced epitope on β1 integrin defined by mAb 15/7. In T cell activation studies using coimmobilized anti-CD3 mAb and the anti-integrin mAbs, the peptide had broader inhibitory activity, suppressing costimulation induced by all the integrin mAbs. The peptide was not generally toxic and was integrin selective in its suppressive activity, as coactivation by ligation of CD3 in conjunction with CD28 or CD26 was not affected. These results suggest that the antagonist peptide CWLDVC can effectively neutralize integrin coactivation systems by a mechanism independent of competitive binding.",
author = "McIntyre, {Bradley W.} and Woodside, {Darren G.} and Caruso, {Denise A.} and Wooten, {David K.} and Simon, {Scott I.} and Sriram Neelamegham and Revelle, {Joanna K.} and Peter Vanderslice",
year = "1997",
month = "5",
day = "1",
language = "English (US)",
volume = "158",
pages = "4180--4186",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "9",

}

TY - JOUR

T1 - Regulation of Human T Lymphocyte Coactivation with an α4 Integrin Antagonist Peptide

AU - McIntyre, Bradley W.

AU - Woodside, Darren G.

AU - Caruso, Denise A.

AU - Wooten, David K.

AU - Simon, Scott I.

AU - Neelamegham, Sriram

AU - Revelle, Joanna K.

AU - Vanderslice, Peter

PY - 1997/5/1

Y1 - 1997/5/1

N2 - The cyclic hexapeptide CWLDVC (TBC 772) is an antagonist of α4 integrins and a potent inhibitor of lymphocyte interactions with fibronectin, vascular cell adhesion molecule-1, and muscosal vascular addressin cell adhesion molecule-1 (MAdCAM-1). As such, peptide TBC 772 effectively inhibits the activation of freshly isolated human T lymphocytes stimulated with purified vascular cell adhesion molecule-1 coimmobilized with anti-CD3 mAb. The influence of peptide binding on distinct sites of the α4β1 complex was determined by flow cytometry and cellular adhesion assays employing a panel of mAbs. Binding of the α4-specific mAb L25 and the β1-specific mAb 33B6 was not altered by the peptide; however, binding of mAb 19H8, which is specific for a combinatorial epitope of α4β1, was dramatically inhibited. Treatment of lymphocytes with the peptide caused an increase in a ligand-induced epitope on β1 integrin defined by mAb 15/7. In T cell activation studies using coimmobilized anti-CD3 mAb and the anti-integrin mAbs, the peptide had broader inhibitory activity, suppressing costimulation induced by all the integrin mAbs. The peptide was not generally toxic and was integrin selective in its suppressive activity, as coactivation by ligation of CD3 in conjunction with CD28 or CD26 was not affected. These results suggest that the antagonist peptide CWLDVC can effectively neutralize integrin coactivation systems by a mechanism independent of competitive binding.

AB - The cyclic hexapeptide CWLDVC (TBC 772) is an antagonist of α4 integrins and a potent inhibitor of lymphocyte interactions with fibronectin, vascular cell adhesion molecule-1, and muscosal vascular addressin cell adhesion molecule-1 (MAdCAM-1). As such, peptide TBC 772 effectively inhibits the activation of freshly isolated human T lymphocytes stimulated with purified vascular cell adhesion molecule-1 coimmobilized with anti-CD3 mAb. The influence of peptide binding on distinct sites of the α4β1 complex was determined by flow cytometry and cellular adhesion assays employing a panel of mAbs. Binding of the α4-specific mAb L25 and the β1-specific mAb 33B6 was not altered by the peptide; however, binding of mAb 19H8, which is specific for a combinatorial epitope of α4β1, was dramatically inhibited. Treatment of lymphocytes with the peptide caused an increase in a ligand-induced epitope on β1 integrin defined by mAb 15/7. In T cell activation studies using coimmobilized anti-CD3 mAb and the anti-integrin mAbs, the peptide had broader inhibitory activity, suppressing costimulation induced by all the integrin mAbs. The peptide was not generally toxic and was integrin selective in its suppressive activity, as coactivation by ligation of CD3 in conjunction with CD28 or CD26 was not affected. These results suggest that the antagonist peptide CWLDVC can effectively neutralize integrin coactivation systems by a mechanism independent of competitive binding.

UR - http://www.scopus.com/inward/record.url?scp=0031136955&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031136955&partnerID=8YFLogxK

M3 - Article

C2 - 9126978

AN - SCOPUS:0031136955

VL - 158

SP - 4180

EP - 4186

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 9

ER -