Researchers have discovered the role played by a key immune-cell coreceptor. CD22 (orange) is a coreceptor to B-cell receptors (BCRs, blue) on the surface of antibody-generating B-cells. CD22 is known to prevent immune responses. But its mechanism of action has been blocked from scientists' view because it binds to immunogenic glycoproteins with sialic acid groups, both from the surrounding medium and on its own cell surface. The cell-surface interactions tie up CD22's binding site, making it hard to study the effects of external CD22 ligands. Laura L. Kiessling and coworkers at the University of Wisconsin, Madison, have now used antigenic polymers bearing both BCR and CD22 ligands (blue circles and red squares) to promote binding of external CD22 ligands (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.0807207106). They find that immunogenic ligands that bind CD22 inhibit immune activation—showing that the presence of sialic acid residues on antigens can suppress the immune response. The work could lead to new strategies to prevent autoimmune conditions like multiple sclerosis.