Recombinant human B7-H4 expressed in Escherichia coli inhibits T lymphocyte proliferation and IL-2 secretion in vitro

Acta Pharmacol Sin. 2006 Jun;27(6):741-6. doi: 10.1111/j.1745-7254.2006.00338.x.

Abstract

Aim: To explore the biofunctions of human B7-H4 generated from prokaryotic system.

Methods: The gene of human B7-H4 extracellular region (IgV-like and IgC-like domains) was obtained by PCR from human cDNA FLJ22418 and then inserted into the prokaryotic expression vector pGEX-5X-3 expressing glutathione s-transferase (GST) fusion protein. After being identified by restriction enzyme digestion and sequencing, the recombinant vector was transferred into host strain E coli BL21-RIL(DE3). A 47 kDa fusion protein (GST/hB7-H4) was induced by isopropyl-beta-D-thiogalactopyranoside (IPTG) and purified by standard methods reported in the prokaryotic system. The inhibitory effect of GST/hB7-H4 on proliferation of T cells was observed in vitro by CD3mAb activated T-cell culturing system and [(3)H]-thymidine incorporation assay. The concentrations of interleukin-2 and iterferon-g in the supernatants of T cells were determined by ELISA.

Results: We successfully constructed the method for high-level expression and purification of the hB7-H4 extracellular domain as GST fusion protein from E coli. The GST/hB7-H4 fusion protein produced in bacteria had obvious biological activity to inhibit T-lymphocyte proliferation and IL-2 secretion.

Conclusion: The prokaryote expression system could be used to generate hB7-H4 protein with natural spatial conformations and biological functions, which provided an efficient and economical way for the preparation of this target protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-1 Antigen / genetics
  • B7-1 Antigen / metabolism
  • B7-1 Antigen / pharmacology*
  • Cell Proliferation / drug effects*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Genetic Vectors
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • Glutathione Transferase / pharmacology
  • Humans
  • In Vitro Techniques
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / pharmacology
  • T-Lymphocytes / cytology*
  • Transduction, Genetic
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1

Substances

  • B7-1 Antigen
  • Interleukin-2
  • Recombinant Fusion Proteins
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1
  • VTCN1 protein, human
  • Interferon-gamma
  • Glutathione Transferase