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## Molecular mimicry and Gram negative infections

The frustrating lack of evidence of infection in many forms of uveitis despite the clinical suspicion and the temporal association of the uveitis with a previous attack of systemic infection is well known to clinical ophthalmologists. The clearest example is the association of acute anterior uveitis with ankylosing spondylitis and Gram negative infections. A recent paper (Nature Medicine 2000;6:215-18) now shows evidence of molecular mimicry in Gram negative infections. Molecular mimicry is the process whereby antigenic epitopes from pathogenic micro-organisms have sufficient similarity to self epitopes that “cross-reactive” infections occur. The mechanism involves dual activation of T cells by the same peptide: one set of T cells being specific for the foreign antigen and the second set being specific for the self antigen. In fact it has been show recently that each T cell receptor is much less selective than previously thought and has the potential to react to many more antigens. In this paper, Loet al have identified an immunodominant epitope derived from the Salmonella typhimurium GroEL molecule. This antigen is was recognised by CD8+ cytotoxic T lymphocytes induced after natural infection. In addition it was presented by the mouse H2-T23 encoded class Ib molecule Qa-1 to the same S typhimurium stimulated cytotoxic T lymphocytes recognising a peptide derived from mouse heat shock protein 60 (presumably) in stressed macrophages. The authors state that their results indicate a mechanism for the aetiological link between Gram negative bacterial infection and autoimmunity.