Interaction of HLA molecules with non-immunological ligands as an explanation of HLA and disease associations.

It is postulated that alloantigens (HLA in particular) may interfere with ligand/receptor interactions not directly involved in immune reactions. This interference may be regarded as a side-effect of the creation of new mutant HLA alleles which are maintained in the population for other reasons. As an example, it is suggested that some HLA molecules may have structures resembling those on receptors for certain hormones which could cause competition between HLA and receptor molecules for the hormone. Facilitation of ligand/receptor interaction may also be envisaged. Such interactions could under certain conditions lead to disease and might explain some associations between HLA and non-immunological diseases (e.g., manic-depressive disease and haemachromatosis).