Uri Galili , Bruce

T h e antibodies that are p roduced in man as a result of specific vaccination or infectious disease comprise only a small propor t ion o f the bulk o f the IgG molecules circulating in the blood. T h e immunity towards these antigens is a t t r ibuted mostly to a relatively high n u m b er o f memory cells and a low titer o f synthesized antibodies. In view of kinetic studies o f ant ibody product ion and the low level o f IgG in the serum of germ-free animals, it is safe to assume that a large propor t ion o f circulating IgG molecules are synthesized as a result of immune reactivity to naturally occurr ing antigens, to which the immune system is constantly exposed. Most o f the known high-titer natural antibodies seem to display ant icarbohydra te specificity. These include the an t i -b lood group A and B antibodies, which interact with GalNAc~I ~ 3(Fuco~l ~ 2)Gal and Gala l 3 [Fuca l ~ 2]Gal (GalNAc, N-acetyl gatactose; Fuc, fucose) 1, respectively (1, 2). Ano the r natural ant ibody with ant icarbohydra te specificity is the ant i-T (Thomsen-Friedenreich) antibody, which binds to Gal/31 ~ 4GalNAc residues (3, 4). It is assumed that these ant icarbohydra te antibodies are constantly p roduced as an immune response to normal gastrointestinal or pulmonary flora that contain bacteria bear ing such antigenic epitopes (1, 3). We have recently (5-7) described a natural IgG ant ibody that appears to contr ibute to extravascular lysis o f normal and some pathological red cells, since it interacts in situ with normal senescent red cells and more extensively with pathological red cells of thalassemia and sickle cell anemia patients. This antibody, designated anti-Gal, was found in high titer in all normal sera tested, independent o f blood type. Fur the rmore , it represents 1% of the total serum IgG. T h e reactivity ofant i-Gal could be assessed by its interaction with c~-galactosyl residues on rabbit red blood cells (RRBC) (8). T o evaluate the s t ructure o f the RRBC antigen recognized by anti-Gai, we have studied its binding to carbohydrate-