[Artificial H-2 dependent carrier determinants of the insulin molecule]

The known tertiary structure of insulin allows the study of carrierdeterminants of insulin: their nature, their distance to antigenic determinants and their H-2 dependance. We examined the influence of "foreign " amino acids of insulins from two different species and the influence of chemically coupled new amino acids at the B-chain of insulin in congenic resistant mice. Three strains were immunized with bovine insulin and three derivatives: LeuB-insulin, LysB-insulin and GluB-insulin. H-2d mice were high responders to insulin and all derivatives, while H-2k mice showed no detectable antibodies. The H-2b strain had an intermediate antibody response to bovine insulin. LeuB-insulin, LysB-insulin and GluB-insulin produced similar titers as unmodified insulin in H-2d mice. In H-2b mice, GluB-insulin produced significantly more antibodies than did all other insulins tested with antibody specificities directed against A8-A10. Therefore Glu at position B0 acts as a carrierdeterminant and A8-A10 as antigenic determinant at the dose utilised in H-2b mice. The distance between both determinants is about 15-20 A, allowing therefore the cooperation of T and B cell.