Molecular basis of human CD22 function and therapeutic targeting

• DOI: 10.1038/s41467-017-00836-6
• Publication Date: 2017-09-26T19:06:58Z
• Authors: June Ereño-Orbea; Taylor Sicard; Hong Cui; Mohammad T. Mazha...; Samir Benlekbir; Alba Guarné; John L. Rubinstein; Jean-Philippe Julien
• Keywords: CD22; Ectodomain

CD22 maintains a baseline level of B-cell inhibition to keep humoral immunity in check. As B-cell-restricted antigen, is targeted therapies against dysregulated B cells that cause autoimmune diseases and blood cancers. Here we report the crystal structure human at 2.1 Å resolution, which reveals specificity for α2-6 sialic acid ligands dictated by pre-formed β-hairpin as unique mode recognition across acid-binding immunoglobulin-type lectins. The ectodomain adopts an extended conformation facilitates concomitant nanocluster formation on binding trans avert autoimmunity mammals. We structurally delineate site therapeutic antibody epratuzumab 3.1 resolution determine critical role N-linked glycosylation engagement. Our studies provide molecular insights into mechanisms governing valuable clues design immune modulators dysfunction.The B-cell-specific co-receptor target depleting cells. authors characterize present its with bound epratuzumab, gives mechanism activation.