Peptide p277 of HSP60 signals T cells: Inhibition of inflammatory chemotaxis

Gabriel Nussbaum, Alexandra Zanin-Zhorov, Francisco Quintana, Ofer Lider, Irun R. Cohen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Peptide p277 is a 24-amino acid fragment of the heat shock protein 60 molecule, first discovered to be an antigen for diabetogenic T-cell clones in non-obese diabetic (NOD) mice. Therapeutic vaccination with p277 can arrest the spontaneous diabetogenic process both in NOD mice and in humans associated with a Th1 to Th2 cytokine shift specific for the autoimmune T cells. We now report that p277 can directly signal human T cells via innate toll-like receptor (TLR)-2, leading to up-regulation of integrin-mediated adhesion to fibronectin, and inhibition of chemotaxis to the chemokine SDF-1α in vitro. Resting CD45RA+ T cells responded to lower concentrations of p277 than resting CD45RO+ T cells, but activation of CD45RO + T cells greatly increased their sensitivity to p277. Mouse T cells, but not macrophages, were also sensitive to the innate effects of peptide p277, and adoptive transfer of diabetes by splenic T cells from NOD mice could be inhibited by p277 treatment before transfer. Thus, T cells do respond innately to p277, and signaling by soluble p277 through TLR2 could contribute to the treatment of type 1 diabetes; p277 may stop the destruction of β cells by signaling in concert both innate and adaptive receptors on T cells.

Original languageAmerican English
Pages (from-to)1413-1419
Number of pages7
JournalInternational Immunology
Volume18
Issue number10
DOIs
StatePublished - Oct 2006
Externally publishedYes

Bibliographical note

Funding Information:
I.R.C. is the incumbent of the Mauerberger Chair of Immunology and the Director of the Center for the Study of Emerging Diseases, Jerusalem. G.N. was supported by a Juvenile Diabetes Research Foundation International post-doctoral fellowship.

Keywords

  • Chemotaxis
  • Delayed-type hypersensitivity
  • Toll-like receptors
  • Type 1 diabetes mellitus

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