HLA-DR, -DQ DNA genotyping and T-cell receptor RFLPs in leprosy

HLA-DR and -DQ restriction fragment length polymorphisms (RFLPs) were examined in Melanesian leprosy patients and controls from New Caledonia. This permitted DNA subtyping of DQw1, a broad serological specificity previously implicated in predisposition to lepromatous leprosy. The DQw1c subtype, found in linkage disequilibrium with DR1, w10, w14, and some Pacific Island variants of DRw6 and DRw8, was significantly reduced in leprosy patients. Since the association between HLA-DR genes and leprosy is not strong, some candidate non-MHC genes for leprosy susceptibility were examined also. T-cell receptor -alpha, -beta, and -gamma gene RFLPs revealed no germ-line defects or major clonal T-cell expansion in either lepromatous or tuberculoid leprosy patients. The human homologue of the murine Ity locus which determines murine susceptibility to Mycobacterium lepraemurium was sought by examining linkage disequilibrium with RFLPs in the human gamma-crystallin genes, since this gene family forms a syntenic group with isocitrate dehydrogenase-1 in both mouse and man and, in the mouse, this cluster is closely linked to the Ity locus. These RFLPs were not associated with leprosy susceptibility in man.