8eb2 | pdb_00008eb2

Structure of HLA-A*02:01 in complex with NY-ESO-1 peptide and PA2.1 Fab

spinqualitylabelsall models 8eb2, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8eb2 is a 15 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.9Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q53Z42_HUMAN Involved in the presentation of foreign antigens to the immune system (By similarity).[SAAS:SAAS003006_004_004364] Publication Abstract from PubMed Innovative cell-based therapies are important new weapons in the fight against difficult-to-treat cancers. One promising strategy involves cell therapies equipped with multiple receptors to integrate signals from more than one antigen. We developed a specific embodiment of this approach called Tmod, a two-receptor system that combines activating and inhibitory inputs to distinguish between tumor and normal cells. The selectivity of Tmod is enforced by the inhibitory receptor (blocker) that recognizes an antigen, such as an HLA allele, whose expression is absent from tumors because of loss of heterozygosity. Although unwanted cross-reactivity of the blocker likely reduces efficacy rather than safety, it is important to verify the blocker's specificity. We have tested an A *02-directed blocker derived from the PA2.1 mouse antibody as a safety mechanism paired with a mesothelin-specific activating CAR in our Tmod construct. We solved the crystal structure of humanized PA2.1 Fab in complex with HLA-A *02 to determine its binding epitope, which was used to bioinformatically select specific class I HLA alleles to test the blocker's functional specificity in vitro. We found that this A *02-directed blocker is highly specific for its cognate antigen, with only one cross-reactive allele (A *69) capable of triggering comparable function. HLA-A *02-gated safety switch for cancer therapy has exquisite specificity for its allelic target antigen.,Mock JY, Winters A, Riley TP, Bruno R, Naradikian MS, Sharma S, Jette CA, Elshimali R, Gahrs C, Toledo-Warshaviak D, West AP Jr, Kamb A, Hamburger AE Mol Ther Oncolytics. 2022 Oct 4;27:157-166. doi: 10.1016/j.omto.2022.09.010. , eCollection 2022 Dec 15. PMID:36381658 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also MHC 3D structures MHC I 3D structures

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