H gene theory of inherited autoimmune disease.

Autoimmune disease in inbred mice is probably determined by co-dominant genes associated with both the major and minor histocompatibility loci. It is postulated that the genes involved are histocompatibility-antigen (H) genes themselves, which delete complementary clones in fetal life, in accord with Burnet's theory of clonal selection. Such deletions cause perturbations in the paratope-idiotope network reactions envisaged by Jerne. As well as having negative effects on immune-response capacity, the perturbations have positive effects, because the deletion of clones with specificity for the idiotopes of other clones permists immune responses which would otherwise be absent. Such perturbations can influence the chance of emergence of a forbidden clone by somatic mutations occurring in the V genes of dividing immunocytes and so can provide a genetic predisposition to autoimmune disease.