Two mechanisms of alloimmunization by RBC transfusions. (A) In the direct pathway of antigen presentation, residual donor leukocytes in the RBC product present endogenous minor histocompatibility antigens to recipient T cells. (B) In the indirect pathway, recipient antigen-presenting cells take up donor RBCs that express minor histocompatibility antigens and process and present these donor epitopes to recipient T cells. Cross-presentation permits exogenous epitopes to be presented in the context of class I MHC antigens.