Insulin-dependent diabetes and human leucocyte antigens.

The association of diabetes with HLA class I alleles in the early 1970s and with HLA class II alleles in the late 1970s provided a crucial, though indirect, indication of the role of immune phenomena in the development of insulin-dependent diabetes mellitus (IDDM). Genotyping of HLA alleles in the mid-1980s opened up a new era. The very precise definition of susceptibility and protection alleles proved to be an important diagnostic factor in predicting IDDM and was also the first step towards an understanding of the role of class II antigen-presenting molecules in the development of the autoimmune reaction responsible for the destruction of insulin-secreting cells and the subsequent onset of diabetes. Animal models have been instrumental in studying the possible relations between the development of IDDM autoimmunity and the expression of particular major histocompatibility complex alleles on a multigenic susceptibility background.