Immunosuppression by co-stimulatory molecules: Inhibition of CD2-CD48/CD58 interaction by peptides from CD2 to suppress progression of collagen-induced arthritis in mice

Ameya Gokhale, Shanthi Kanthala, John Latendresse, Veena D Taneja, Seetharama Satyanarayanajois

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Targeting co-stimulatory molecules to modulate the immune response has been shown to have useful therapeutic effects for autoimmune diseases. Among the co-stimulatory molecules, CD2 and CD58 are very important in the early stages of generation of an immune response. Our goal was to utilize CD2-derived peptides to modulate protein-protein interactions between CD2 and CD58, thereby modulating the immune response. Several peptides were designed based on the structure of the CD58-binding domain of CD2 protein. Among the CD2-derived peptides, peptide 6 from the F and C β-strand region of CD2 protein exhibited inhibition of cell-cell adhesion in the nanomolar concentration range. Peptide 6 was evaluated for its ability to bind to CD58 in Caco-2 cells and to CD48 in T cells from rodents. A molecular model was proposed for binding a peptide to CD58 and CD48 using docking studies. Furthermore, in vivo studies were carried out to evaluate the therapeutic ability of the peptide to modulate the immune response in the collagen-induced arthritis (CIA) mouse model. In vivo studies indicated that peptide 6 was able to suppress the progression of CIA. Evaluation of the antigenicity of peptides in CIA and transgenic animal models indicated that this peptide is not immunogenic.

Original languageEnglish (US)
Pages (from-to)106-118
Number of pages13
JournalChemical Biology and Drug Design
Volume82
Issue number1
DOIs
StatePublished - Jul 2013

Fingerprint

Experimental Arthritis
Immunosuppression
Collagen
Peptides
Molecules
Proteins
Genetically Modified Animals
Molecular Models
Caco-2 Cells
Therapeutic Uses
T-cells
Cell adhesion
Cell Adhesion
Autoimmune Diseases
Rodentia
Animal Models
Animals
T-Lymphocytes
Cells

Keywords

  • CD2
  • CD58
  • Collagen-induced arthritis
  • Cyclic peptide
  • Docking
  • Immune response
  • Protein-protein interaction

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Immunosuppression by co-stimulatory molecules : Inhibition of CD2-CD48/CD58 interaction by peptides from CD2 to suppress progression of collagen-induced arthritis in mice. / Gokhale, Ameya; Kanthala, Shanthi; Latendresse, John; Taneja, Veena D; Satyanarayanajois, Seetharama.

In: Chemical Biology and Drug Design, Vol. 82, No. 1, 07.2013, p. 106-118.

Research output: Contribution to journalArticle

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