classification of human blood based on the presence of antigens (antigen) I and i on the surface of red blood cells (erythrocyte). The Ii blood group system is associated with cold antibodies (antibody) (antibodies that function only at temperatures below normal body heat) and several blood diseases (blood disease).

The I antigen is found in the cell membrane (cell) of red blood cells in all adults, whereas the i antigen is found only on red blood cells of the developing fetus and newborn infants. In newborn infants the i antigen undergoes gradual conversion to reach adult levels of the I antigen within 18 months of birth. The formation of the I antigen from the i antigen in red blood cells is catalyzed by a protein called I-branching enzyme. Rare variants of the i antigen exist; for example, the antigen i₁ is found as a rarity in whites, and the antigen i₂ is found as a rarity mostly among blacks. Natural antibodies to I are found in adults who possess the i antigen; the presence of the i antigen in adults is caused by mutation of a gene known as GCNT2, which encodes the I-branching enzyme.

Auto-antibodies to I are the commonest source of cold antibodies in acquired hemolytic anemia. Auto-antibodies to i have been identified in persons with leukemia and other blood diseases; a transient auto-anti-i is relatively common in people with infectious mononucleosis.