Two integrin-binding peptides abrogate T cell-mediated immune responses in vivo

Thomas A. Ferguson, Hitoshi Mizutani, Thomas S. Kupper

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

Abstract

Two VLA protems (or β1 integrins; originaly 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-ProGlu-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 mumme response in a marine 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.

Original languageEnglish
Pages (from-to)8072-8076
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number18
DOIs
StatePublished - 1991

Keywords

  • Contact hapersensitivity
  • Fibronectin
  • Originally very late activation antigen
  • VLA

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