Abstract: Red blood cell (RBC) alloimmunization is a significant immunological concern in clinical transfusion. It refers to the immune response wherein the recipient recognizes foreign RBC antigens and produces specific antibodies, potentially leading to hemolytic transfusion reactions or hemolytic disease of the fetus and newborn in severe cases. This immune process is possible dependent on the antigen presentation mechanism mediated by HLA class Ⅱ molecules, involving the presentation of antigens by dendritic cells, recognition and activation by CD4⁺ T cells, and subsequent help to produce IgG antibody by B cells. Whether an individual develops antibodies upon exposure to alloantigens is closely related to dosage,their immune status, inflammatory environment, and genetic background. The high polymorphism of HLA class Ⅱ genes underlies the inter-individual variability in immune responses to specific RBC antigens. Certain alleles, such as HLA-DRB1^*04 and DRB1^*15, have been shown to enhance peptide presentation capabilities, significantly increasing the risk of antibody formation. In contrast, some HLA class Ⅱ alleles may exhibit protective effects. Here we systematically reviewed the association and potential mechanisms between HLA class Ⅱ genes, represented by HLA-DRB1 and HLA-DQ, and the development of RBC alloantibodies. The aim is to provide a theoretical basis for individualized transfusion strategies and immune risk prediction in clinical practice.

Key words: Red blood cells, Alloimmune antibodies, HLA, Gene polymorphism