Responsiveness of HLA-DR15 transgenic mice to immunization with purified RhD protein. A representative example is shown (n = 12). RhD-immunized HLA-DR15 transgenic mice produce serum antibodies that bind to human RBCs, as detected by IELAT (A) and agglutination (B). Most such antibodies bind to RhD-positive, but not to -negative, RBCs. Splenocytes isolated from RhD-immunized mice proliferate in vitro in response to stimulation with the RhD protein (▪) compared with unstimulated control cultures (□) (C). There is no proliferative response to RhD protein by splenocytes isolated from PBS-immunized control mice. Error bars represent SD of triplicates.