Anti-RBC mAbs cross-enhance to third-party alloantigens only if they are expressed on the same RBCs. Recipient B6 mice were pretreated with either PBS, anti-HOD mAb, or anti-K mAb. For each pretreatment, 4 different groups were set up, each receiving a different RBC transfusion: HOD RBCs, K RBCs, HOD RBCs mixed with K RBCs (HOD+K), or F1 RBCs expressing both alloantigens. Serum was obtained 21 days after transfusion and was assayed for polyclonal anti-HOD antibodies (A) and polyclonal anti-K antibodies (B) by indirect immunofluorescence using HOD or K RBC targets, respectively. Data were analyzed with a 1-way ANOVA using a Dunnett multiple comparison test to the control PBS group. *P ≤ .05; ****P ≤ .0001.