9OA9

CryoEM structure of anti-MHC-I mAb B1.23.2 Fc domains

Summary for 9OA9

• Entry DOI: 10.2210/pdb9oa9/pdb
• EMDB information: 46601 46602 70276
• Descriptor: Anti-MHC-I mAb B1.23.2 Fc domains H-chain, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-4)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: mhc-i, hla, anti-human-mab, h2-dd, b1.23.2, anti-mhc-i antibody, anti-tumor, cancer immunotherapy, antitumor protein
• Biological source: Homo sapiens
• Total number of polymer chains: 2
• Total formula weight: 99240.92

Authors

Jiang, J.,Natarajan, K.,Margulies, D.H. (deposition date: 2025-04-20, release date: 2026-02-04, Last modification date: 2026-03-18)

Primary citation

Jiang, J.,Panda, A.K.,Natarajan, K.,Lei, H.,Sharma, S.,Boyd, L.F.,Towler, R.R.,Chempati, S.,Ahmad, J.,Morton, A.J.,Lang, Z.C.,Sun, Y.,Sgourakis, N.,Meier-Schellersheim, M.,Huang, R.K.,Shevach, E.M.,Margulies, D.H.
Structural mechanism of anti-MHC-I antibody blocking of inhibitory NK cell receptors in tumor immunity.
Commun Biol, 9:-, 2026

PubMed Abstract: 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 α2 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.

PubMed: 41629525
DOI: 10.1038/s42003-026-09641-8

Experimental method

ELECTRON MICROSCOPY (3.44 Å)