Minor Antigens on Transfused RBCs Crossprime CD8 T Cells but Do Not Induce Full Effector Function

HLA‐matched bone marrow transplantation (BMT) is a cure for nonmalignant hematological disorders; however, rejection rates are high and correlate with the number of antecedent transfusions. Recently, using murine models, we reported that minor antigens (mHAs) in transfused leukoreduced red blood cell (RBC) or platelet units induce rejection of subsequent BMT. To study RBCs as an immunogen, we utilized transgenic donors that express a model mHA selectively on RBCs (HOD mouse). Transfusion of HOD blood did not induce BMT rejection of marrow that shared mHAs with the HOD RBCs. Similarly, no endogenous anti‐HOD CD8+ T‐cell response was detected with antigen‐specific tetramer reagents. Adoptively transferred OT‐I T cells rapidly expanded after HOD blood transfusion; however, only a semi‐effector phenotype was observed (tumor necrosis factor‐α and interferon‐γ secretion, but essentially no Granzyme B). After initial expansion, OT‐I T cells contracted rapidly to very low levels. A similar trend was observed by in vivo CTL assay, with only transient lytic activity. Together, these data indicate that RBCs may not be the component of RBC units that induces BMT rejection, and suggest that contaminating platelets or leukocytes may be responsible. Minor alloantigens on transfused RBCs are cross‐presented to recipient CD8+ T cells and result in activation and proliferation, but do not induce a full effector phenotype or promote BMT rejection.