We describe three human proliferating T cell colonies, derived from mixed leukocyte culture with a non-diabetic individual (DR3 + 4) as the source of responding cells and an insulin-dependent diabetic patient (also DR3 + 4) as the source of stimulating cells. One colony detects HLA-Dw10 or a closely related antigen, and two detect an antigen that we call BO1 (Boston 1). BO1 is found so far on cells of all persons with DR5, about half of those with DRw6, and a particular subset of those with DR3. Among DR3-positive subjects, BO1 is positively correlated with HLA-B18 and BfF1, and negatively correlated with HLA-B8. These findings suggest that BO1 occurs in linkage disequilibrium with DR5, DRw6, and the haplotype B18, BfF1, DR3, the latter being common in southern Europe and reported previously to be a marker for insulin-dependent diabetes. In limited testing (21 subjects), BO1 was completely included in the supertypic specificity MT2, BO1 is a Class II HLA antigen, as demonstrated by blocking with monoclonal antibodies, but is distinct from all known antigens of the DR, MB(DC), MT, and SB series. It could be located on the same polypeptide chain as one or more of these antigen groups, however, particularly DR and/or MT.