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Publication Abstract from PubMed

CD22 maintains a baseline level of B-cell inhibition to keep humoral immunity in check. As a B-cell-restricted antigen, CD22 is targeted in therapies against dysregulated B cells that cause autoimmune diseases and blood cancers. Here we report the crystal structure of human CD22 at 2.1 A resolution, which reveals that specificity for alpha2-6 sialic acid ligands is dictated by a pre-formed beta-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins. The CD22 ectodomain adopts an extended conformation that facilitates concomitant CD22 nanocluster formation on B cells and binding to trans ligands to avert autoimmunity in mammals. We structurally delineate the CD22 site targeted by the therapeutic antibody epratuzumab at 3.1 A resolution and determine a critical role for CD22 N-linked glycosylation in antibody engagement. Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells. Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation.

Molecular basis of human CD22 function and therapeutic targeting.,Ereno-Orbea J, Sicard T, Cui H, Mazhab-Jafari MT, Benlekbir S, Guarne A, Rubinstein JL, Julien JP Nat Commun. 2017 Oct 2;8(1):764. doi: 10.1038/s41467-017-00836-6. PMID:28970495^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.