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C. Superantigen

Several infectious agents (ie. Mouse mammary tumour virus) contain antigens with the ability to polyclonally activate a subset of CD4+ T cells bearing particular V TCR families

Hypothesis is that this may activate autoreactive cells

If this were true, we would expect to see > of certain V in autoimmune lesions

Isolated reports in rheumatoid arthritis and diabetes

No strong evidence

D.  Cross reaction

Cross reaction of peptide present in micro-organism with self peptide present in the host

Coxsackie virus peptide contains homology to a T cell epitope in GAD which is recognised by a subset of patients with type I diabetes

B. Immune stimulation

   Inappropriate MHC II expression

   High level of APCs with “second signal” breaks anergy

   Activation of T and B responses to self Ag

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