9D72
CryoEM structure of anti-MHC-I Fab M1/42 complex with H2-Dd
Summary for 9D72
| Entry DOI | 10.2210/pdb9d72/pdb |
| Related | 8TQ4 |
| EMDB information | 46600 |
| Descriptor | Beta-2-microglobulin, Fab M1/42 Light Chain, Surface protein gp120, ... (5 entities in total) |
| Functional Keywords | mhc-i, anti-mouse-mab, h2-dd, m1/42, anti-mhc-i antibody, anti-tumor, cancer immunotherapy, antitumor protein, antitumor protein-immune system complex, antitumor protein/immune system |
| Biological source | Mus musculus (house mouse) More |
| Total number of polymer chains | 5 |
| Total formula weight | 91734.50 |
| Authors | Jiang, J.,Natarajan, K.,Margulies, D.H.,Lei, H.,Huang, R. (deposition date: 2024-08-16, 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 Cited by 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: 41629525DOI: 10.1038/s42003-026-09641-8 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.67 Å) |
Structure validation
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