A retro-inverso peptide mimic of CD28 encompassing the MYPPPY motif adopts a polyproline type II helix and inhibits encephalitogenic T cells in vitro

Mythily Srinivasan, R. M. Wardrop, I. E. Gienapp, S. S. Stuckman, C. C. Whitacre, P. T P Kaumaya

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Complete activation of T cells requires two signals: an Ag-specific signal delivered via the TCR by the peptide-MHC complex and a second costimulatory signal largely provided by B7:CD28/CTLA-4 interactions. Previous studies have shown that B7 blockade can either ameliorate experimental autoimmune encephalomyelitis by interfering with CD28 signaling or exacerbate the disease by concomitant blockade of CTLA-4 interaction. Therefore, we developed a functional CD28 mimic to selectively block B7:CD28 interactions. The design, synthesis, and structural and functional properties of the CD28 free peptide, the end group-blocked CD28 peptide, and its retro-inverso isomer are shown. The synthetic T cell-costimulatory receptor peptides fold into a polyproline type II helical structure commonly seen in regions of globular proteins involved in transient protein-protein interactions. The binding determinants of CD28 can be transferred onto a short peptide mimic of its ligand-binding region. The CD28 peptide mimics effectively block the expansion of encephalitogenic T cells in vitro suggesting the potential usefulness of the peptides for the treatment of autoimmune disease conditions requiring down-regulation of T cell responses.

Original languageEnglish (US)
Pages (from-to)578-585
Number of pages8
JournalJournal of Immunology
Volume167
Issue number1
StatePublished - Jul 1 2001
Externally publishedYes

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T-Lymphocytes
Peptides
Artificial Cells
Proteins
Autoimmune Experimental Encephalomyelitis
T-Cell Antigen Receptor
In Vitro Techniques
polyproline
Autoimmune Diseases
Down-Regulation
Ligands

ASJC Scopus subject areas

  • Immunology

Cite this

A retro-inverso peptide mimic of CD28 encompassing the MYPPPY motif adopts a polyproline type II helix and inhibits encephalitogenic T cells in vitro. / Srinivasan, Mythily; Wardrop, R. M.; Gienapp, I. E.; Stuckman, S. S.; Whitacre, C. C.; Kaumaya, P. T P.

In: Journal of Immunology, Vol. 167, No. 1, 01.07.2001, p. 578-585.

Research output: Contribution to journalArticle

Srinivasan, Mythily ; Wardrop, R. M. ; Gienapp, I. E. ; Stuckman, S. S. ; Whitacre, C. C. ; Kaumaya, P. T P. / A retro-inverso peptide mimic of CD28 encompassing the MYPPPY motif adopts a polyproline type II helix and inhibits encephalitogenic T cells in vitro. In: Journal of Immunology. 2001 ; Vol. 167, No. 1. pp. 578-585.
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AU - Gienapp, I. E.

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AU - Whitacre, C. C.

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