6DDV

Crystal Structure Analysis of the Epitope of an Anti-MICA Antibody

6DDV の概要

• エントリーDOI: 10.2210/pdb6ddv/pdb
• 分子名称: Anti-MICA Fab fragment heavy chain clone 6E1, MHC class I chain-related protein A, Anti-MICA Fab fragment light chain clone 6E1, ... (4 entities in total)
• 機能のキーワード: fab fragment-antigen complex, immunoglobulin domain, immune system
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 58915.51

構造登録者

Matsumoto, M.L. (登録日: 2018-05-10, 公開日: 2018-10-24, 最終更新日: 2024-10-16)

主引用文献

Lombana, T.N.,Matsumoto, M.L.,Berkley, A.M.,Toy, E.,Cook, R.,Gan, Y.,Du, C.,Schnier, P.,Sandoval, W.,Ye, Z.,Schartner, J.M.,Kim, J.,Spiess, C.
High-resolution glycosylation site-engineering method identifies MICA epitope critical for shedding inhibition activity of anti-MICA antibodies.
MAbs, 11:75-93, 2019

PubMed Abstract: As an immune evasion strategy, MICA and MICB, the major histocompatibility complex class I homologs, are proteolytically cleaved from the surface of cancer cells leading to impairment of CD8 + T cell- and natural killer cell-mediated immune responses. Antibodies that inhibit MICA/B shedding from tumors have therapeutic potential, but the optimal epitopes are unknown. Therefore, we developed a high-resolution, high-throughput glycosylation-engineered epitope mapping (GEM) method, which utilizes site-specific insertion of N-linked glycans onto the antigen surface to mask local regions. We apply GEM to the discovery of epitopes important for shedding inhibition of MICA/B and validate the epitopes at the residue level by alanine scanning and X-ray crystallography (Protein Data Bank accession numbers 6DDM (1D5 Fab-MICA*008), 6DDR (13A9 Fab-MICA*008), 6DDV (6E1 Fab-MICA*008). Furthermore, we show that potent inhibition of MICA shedding can be achieved by antibodies that bind GEM epitopes adjacent to previously reported cleavage sites, and that these anti-MICA/B antibodies can prevent tumor growth in vivo.

PubMed: 30307368
DOI: 10.1080/19420862.2018.1532767

実験手法

X-RAY DIFFRACTION (2.05 Å)