Notably absent from Figure 1 is the association between HLA and type 1 diabetes (T1D). This was first described as an association with ‘B15’ in 1973 (ref. 14), later also with B8, and then, in 1975 (ref. 15), as an association with Dw3 and Dw4 defined by mixed lymphocyte culture typing. The latter became an association with the HLA-DR3 and HLA-DR4 serological determinants in 1977. Winearls et al.16 observed that the association between B15 and DR4 was much stronger in individuals with T1D than in controls, in contrast to the association between B8 and DR3, which was the same in both affected individuals and controls. This, together with the observation that the T1D association was strongest in DR3/DR4 heterozygotes, suggested that the association was most probably with DQ, as this was the only product both of whose chains were polymorphic, thus allowing the possibility of association with a particular heterozygous combination at the DQ locus. The association with DQ was subsequently established in 1987 (ref. 17).
