Two integrin-binding peptides abrogate T cell-mediated immune responses in vivo.
Two VLA proteins (or beta 1 integrins; originally called very late activation antigens) that bind to distinct determinants on fibronectin (FN) are increased on activated immune or memory T cells. VLA-4 binds to the peptide sequence Gly-Pro-Glu-Ile-Leu-Asp-Val-Pro-Ser-Thr (GPEILDVPST in single-letter code) on the alternatively spliced CS-1 form of FN, whereas VLA-5 binds to an Arg-Gly-Asp sequence found on all forms of FN. It has been proposed that the migration of immune T cells out of blood vessels and through connective tissue to a site of antigenic challenge is facilitated by the interaction of such integrins with matrix protein molecules. We have examined directly the role of T-cell integrins in vivo by using the well-characterized, T-cell-mediated contact hypersensitivity (CHS) response to the hapten trinitrochlorobenzene (TNCB). We demonstrate that the cells that transfer CHS to TNCB adhere to FN in the presence of Ca2+/Mg2+, and T-cell populations depleted of FN-adherent cells do not transfer immunity. We further show that TNCB-immune T cells treated with the synthetic peptides GPEILDVPST or Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP in single-letter code), ligands for VLA-4 and VLA-5, respectively, lose their ability to mediate this immune response in a murine model, whereas the control peptides Val-Ile-Pro-Asp-Leu-Thr-Glu-Ser-Pro-Gly and Gly-Arg-Gly-Glu-Ser-Pro have no effect. Neither GPEILDVPST nor GRGDSP significantly inhibited the proliferative response of TNCB-immune T cells in vitro. These data suggest that FN-binding integrins on T cells play a role in the localization of T cells to sites of antigenic challenge in tissue.
Ferguson
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Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Mizutani
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Kupper
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D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D003877:Dermatitis, Contact / Q000276:immunology / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D007111:Immunity, Cellular; D016023:Integrins / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D016029:Receptors, Very Late Antigen / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016023:Integrins; D010455:Peptides; D016029:Receptors, Very Late Antigen