alpha-Galactosyl antibody redistributes alpha-Galactosyl at the surface ofpig blood and endothelial cells

The interaction of antibodies with cell surface antigens may induce redistr ibution of immune complexes, followed by antigen depletion, with increased resistance to injurious effect of antibody and complement (antigenic modula tion). Human natural antibodies to Gal alpha 1,3Gal beta 1,4GlcNAc-R (alpha Gal) epitopes expressed at the surface of pig cells are a major obstacle t o xenotransplantation. Recent studies have shown that these antibodies do n ot modulate alpha Gal, but the morphological consequences of the antigen-an tibody interaction are unknown. Pig blood and endothelial cells, were expos ed to baboon alpha-Gal antibodies, and studied by immunofluorescence and ph ase contrast microscopy, flow cytometry, and inhibition enzyme-linked immun osorbent assay. In cells studied at 4 degrees C or fixed, alpha Gal was dif fusely expressed at the surface. After cross-linking at 37 degrees C, antig enic modulation did not occur, but granular redistribution of alpha Gal imm une complexes was seen in all cell types. In other systems a similar redist ribution is known to induce perturbation of the plasma membrane/cytoskeleta l structure with changes in adhesive properties, gene regulation, and T cel l activation, which could be important if pig xenografts will be made to su rvive for prolonged periods.