Investigation for Autoreactive T-cell to Autoantigen in Behcet's Disease

Research Project

Project/Area Number	10671658
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Ophthalmology
Research Institution	Tokyo Medical University
Principal Investigator	TANAKA Takao Tokyo Medical University, Ophthalmology, Assistant Professor, 医学部, 講師 (40207105)
Project Period (FY)	1998 – 1999
Project Status	Completed (Fiscal Year 1999)
Budget Amount *help	¥2,400,000 (Direct Cost: ¥2,400,000) Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000) Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywords	Behcet's disease / Streptococcus / Heat-shock protein / Amino acid sequence / Experimental Uveitis / みどり膜炎 / 熱ショックタンパク質HSP / 溶連菌HSP60 / 網膜HSP60
Research Abstract	The observation of recurrent oral aphtha preceding ocular inflammation in patients with Behcet's disease suggests a role of oral Streptococcus in the etiology of this disease. Heat-treated Streptoccus antigen can induce ocular inflammation or systemic symptoms in Behcet's disease patients. Furthermore, the presence of an autoantibody against retinat heat-shock protein 60 (HSP60) has been detected in the sera of these patients. Injection of extracted retinal HSP60 also induces experimental uveitis in treated rats. The characteristics of retinal HSP60 and HSP60 from Streptoccus pyogenes (S. pyogenes) were evaluated using a molecular biological approach. The gene encoding HSP60 was isolated by polymerase chain reaction from a bovine retinal cDNA library and from S. pyogenes DNA. The DNA sequence of the HSP60 coding region was determined, and the amino acid sequences of the encoded proteins were predicted from the DNA sequence. The synthetic peptide (50 nmol) was emulsified with Freund's complete adjuvant and injected into rats. Comparison of the amino acid sequences of Streptococcal and bovine retinal HSP60 revealed about 200 residue region with 47% homology. Experimental uveitis was mainly induced in rats inoculated with retinal HSP60-derived peptide or Streptococcus HSP60-derived peptide that is equivalent to residues 245-259 of human HSP65. Retinal and Streptococcal HSP60 amino acid composition are thought to be important and useful for investigating the mechanisms involved in the induction of Behcet's disease.