9d74

CryoEM structure of anti-MHC-I Fab B1.23.2 complex with HLA-B44:05

spinqualitylabelsall models 9d74, resolution 3.31Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9d74 is a 5 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.31Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q860B7_HUMAN Publication Abstract from PubMed Anti-major histocompatibility complex class I (MHC-I) mAbs can stimulate immune responses to tumors and infections by blocking suppressive signals delivered via various immune inhibitory receptors. To understand such functions, we determined the structure of a highly cross-reactive anti-human MHC-I mAb, B1.23.2, in complex with the MHC-I molecule HLA-B*44:05 by both cryo-electron microscopy (cryo-EM) and X-ray crystallography. Structural models determined by the two methods were essentially identical revealing that B1.23.2 binds a conserved region on the alpha2(1) helix that overlaps the killer immunoglobulin-like receptor (KIR) binding site. Structural comparison to KIR/HLA complexes reveals a mechanism by which B1.23.2 blocks inhibitory receptor interactions, leading to natural killer (NK) cell activation. B1.23.2 treatment of the human KLM-1 pancreatic cancer model in humanized (NSG-IL15) mice provides evidence of suppression of tumor growth. Such anti-MHC-I mAb that block inhibitory KIR/HLA interactions may prove useful for tumor immunotherapy. Structural mechanism of anti-MHC-I antibody blocking of inhibitory NK cell receptors in tumor immunity.,Jiang J, Panda AK, Natarajan K, Lei H, Sharma S, Boyd LF, Towler RR, Chempati S, Ahmad J, Morton AJ, Lang ZC, Sun Y, Sgourakis N, Meier-Schellersheim M, Huang RK, Shevach EM, Margulies DH Commun Biol. 2026 Feb 2. doi: 10.1038/s42003-026-09641-8. PMID:41629525 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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