Affordable Access

Regulation of T cell response by blocking the ICOS signal with the B7RP-1-specific small antibody fragment isolated from human antibody phage library.

Authors
  • Maeda, Masatoshi1
  • Ito, Yuji
  • Hatanaka, Takaaki
  • Hashiguchi, Shuhei
  • Torikai, Masaharu
  • Nakashima, Toshihiro
  • Sugimura, Kazuhisa
  • 1 Department of Chemistry, Biotechnology and Chemical Engineering, Graduate School of Science and Engineering, Kagoshima University, Kagoshima, Kagoshima, Japan. , (Japan)
Type
Published Article
Journal
mAbs
Publisher
Landes Bioscience
Publication Date
Jan 01, 2009
Volume
1
Issue
5
Pages
453–461
Identifiers
PMID: 20065650
Source
Medline
Language
English
License
Unknown

Abstract

A costimulatory signal is required for the full activation of T cells, in addition to the antigen-specific signal via the T cell receptor. The inducible costimulator, ICOS is one of the costimulatory molecules that play an essential role in this process, particularly in the expansion or the development of effector T cells. As blocking of the interaction between ICOS and its ligand, B7RP-1, suppresses the T cell response, it can be applied to the treatment of allograft rejection or autoimmune diseases. Here, we isolated four scFv clones that were specific to human B7RP-1 by biopanning a human antibody phage library. We found that three of these clones inhibited the interaction between ICOS-Fc and B7RP-1-Fc. These inhibitory clones not only recognized B7RP-1 molecules expressed on B cells, as assessed by FACS, but also exhibited inhibitory activity in a proliferation assay of T cells stimulated with anti-CD3 mAb and B7RP-1-Fc. Finally, the suppression effect of the scFv on the allogenic immune response was examined using a mixed lymphocyte reaction assay, which demonstrated a successful inhibition of the allogenic reaction, in spite of the high dose needed for complete inhibition (360 nM).

Report this publication

Statistics

Seen <100 times