The Role of Heat Shock Protein, Microbial and Autoimmune Agents in the Aetiology of Behget's Disease

Investigation of the aetiology of Behçet's disease (BD) has focused predominantly on herpes simplex virus immunopathology, autoimmunity to oral mucosa or cross-reactive microbial antigens, and streptococcal infection. These aetiological factors might have a common denominator in microbial heat shock protein (HSP) which shows significant homology with the human mitochondrial HSP. Indeed, the uncommon serotypes of Streptococcus sanguis found in BD cross-react with the 65 kD HSP which also shares antigenicity with an oral mucosal antigen. T cell epitope mapping has identified 4 peptides derived from the sequence of the 65 kD HSP which stimulate specifically TCR gamma delta + lymphocytes from patients with BD. These peptides (111-125, 154-172, 219-233 and 311-325) show significant homology with the corresponding peptides derived from the human 60 kD HSP. The specific proliferative response of TCR gamma delta + lymphocytes elicited by the 4 peptides can be used as a laboratory test for the diagnosis of BD. The pathogenic significance of these peptides has been established by inducing uveitis in rats.