Herpes simplex virus-induced keratitis: Evaluation of the role of molecular mimicry in lesion pathogenesis

Viruses are suspected but usually unproven triggering factors in autoimmuni ty. One favored mechanism to explain the role of viruses in the genesis of autoimmunity is molecular mimicry. An immunoinflammatory blinding lesion ca lled herpetic stromal keratitis (HSK) that follows ocular infection with he rpes simplex virus (HSV) is suggested to result from a CD4(+) T-cell respon se to a UL6 peptide of HSV that cross-reacts with a corneal autopeptide sha red with the immunoglobulin G2a(b) (IgG2a(b)) isotype, The present report r eevaluates the molecular mimicry hypothesis to explain HSK pathogenesis, Ou r results failed to reveal cross-reactivity between the UL6 and IgG2ab pept ides or between peptide reactive T cells and HSV antigens, More importantly , animals infected with HSV failed to develop responses that reacted with e ither peptide, and infection with a recombinant vaccinia UL6 vector failed to cause HSK, in spite of generating UL6 reactivity, Other lines of evidenc e also failed to support the molecular mimicry hypothesis, such as the fail ure to affect HSK severity upon tolerization of susceptible BALB/c and B-ce ll-deficient mice with IgG2ab or UL6 peptides, An additional study system r evealed that HSK could be induced in mouse strains, such as the OT2 x RAG1( -/-) mice (T cell receptor transgenic recognizing OVA(323-339)) that were u nable to produce CD4(+) T-cell responses to any detectable HSV antigens, Ou r results cast doubt on the molecular mimicry hypothesis as an explanation for the pathogenesis of HSK and indicate that if autoimmunity is involved i ts likely proceeds via a bystander activation mechanism.