High-affinity ligand probes of CD22 overcome the threshold set by cis ligands for binding, endocytosis, and killing of B cells | |
Collins, B. E. ; Blixt, O. ; Han, S. F. ; Duong, B. ; Li, H. Y. ; Nathan, J. K. ; Bovin, N. ; Paulson, J. C. ; Han SF(韩守法) | |
2006 | |
关键词 | NON-HODGKINS-LYMPHOMA MYELIN-ASSOCIATED GLYCOPROTEIN HUMANIZED ANTI-CD22 ANTIBODY N-GLYCOLYLNEURAMINIC ACID SIALIC-ACID IMMUNOGLOBULIN SUPERFAMILY MONOCLONAL-ANTIBODY PROTEIN CD22 BONE-MARROW MURINE CD22 |
英文摘要 | CD22 (Siglec-2) is a key regulator of B cell signaling whose function is modulated by interaction with extracellular glycan ligands mediated through its N-terminal Ig domain. Its preferred ligand is the sequence Sia alpha 2-6Gal that is abundantly expressed on N-linked glycans of B cell glycoproteins, and by binding to CD22 in cis causes CD22 to appear "masked" from binding to synthetic sialoside probes. Yet, despite the presence of cis ligands, CD22 redistributes to sites of cell contact by binding to trans ligands on neighboring cells. In this study, we demonstrate the dynamic equilibrium that exists between CD22 and its cis and trans ligands, using a high-affinity multivalent sialoside probe that competes with cis ligands and binds to CD22 on native human and murine B cells. Consistent with the constitutive endocytosis reported for CD22, the probes are internalized once bound, demonstrating that CD22 is an endocytic receptor that can carry ligand-decorated "cargo" to intracellular compartments. Conjugation of the sialoside probes to the toxin saporin resulted in toxin uptake and toxin-mediated killing of B lymphoma cell lines, suggesting an alternative approach for targeting CD22 for treatment of B cell lymphomas. |
语种 | 英语 |
内容类型 | 期刊论文 |
源URL | [http://dspace.xmu.edu.cn/handle/2288/64284] ![]() |
专题 | 化学化工-已发表论文 |
推荐引用方式 GB/T 7714 | Collins, B. E.,Blixt, O.,Han, S. F.,et al. High-affinity ligand probes of CD22 overcome the threshold set by cis ligands for binding, endocytosis, and killing of B cells[J],2006. |
APA | Collins, B. E..,Blixt, O..,Han, S. F..,Duong, B..,Li, H. Y..,...&韩守法.(2006).High-affinity ligand probes of CD22 overcome the threshold set by cis ligands for binding, endocytosis, and killing of B cells.. |
MLA | Collins, B. E.,et al."High-affinity ligand probes of CD22 overcome the threshold set by cis ligands for binding, endocytosis, and killing of B cells".(2006). |
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