8TQ5

Crystal structure of Fab DX17 in complex with MHC-I (HLA-B*44:05)

Summary for 8TQ5

• Entry DOI: 10.2210/pdb8tq5/pdb
• Related: 8TQ4 8TQ6 8TQ7 8TQ8 8TQ9 8TQA
• Descriptor: HLA class I histocompatibility antigen B alpha chain (HLA-B*44:05), Beta-2-microglobulin, MHC class II antigen, ... (7 entities in total)
• Functional Keywords: histocompatibility complex class i, mhc-i, immune response, immune system fab, antibody, anti-mhc antibody, cancer tumor, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 92465.79

Authors

Jiang, J.,Natarajan, K.,Boyd, L.F.,Margulies, D.H. (deposition date: 2023-08-06, release date: 2025-02-05, Last modification date: 2025-10-08)

Primary citation

Panda, A.K.,Natarajan, K.,Sinha, S.,Jiang, J.,Chempati, S.,Boyd, L.F.,Desai, P.P.,Buszko, M.,Kim, Y.H.,Kazmi, S.,Fisk, B.,Teke, M.E.,Larrain, C.M.,Remmert, K.,Blakely, A.M.,Douagi, I.,Hernandez, J.M.,Margulies, D.H.,Shevach, E.M.
Antibody Mediated Inhibition of HLA/LILR Interactions Breaks Innate Immune Tolerance and Induces Antitumor Immunity.
Cancer Immunol Res, 2025

PubMed Abstract: Immune checkpoint blockade for the treatment of malignancies has been focused on reversing inhibitory pathways in T lymphocytes. NK cells are a potent innate defense against tumors and virally infected cells, but their therapeutic manipulation for anticancer immunity has been inadequately explored. Considerable attention has been focused on approaches to blocking inhibitory receptors on NK and myeloid cells. Most effort has been directed to the killer immunoglobulin-like receptors and CD94/NKG2A on NK cells. Another set of receptors with similar function in both NK cells and myeloid cells is the leukocyte immunoglobulin-like receptors (LILR) that interact with a wide variety of HLA molecules. Using pan-anti-HLA mAbs that recognize a conserved epitopic region on HLA also seen by LILRs, we investigated their functional effects in several models of tumor immunity. The pan-anti-HLA mAbs blocked the binding of most LILRs and did not block killer cell immunoglobulin-like receptors or CD94/NKG2A/C or T-cell receptor recognition. They also activated dysfunctional NK cells explanted from a variety of human cancers and resulted in enhancement of tumor immunity in humanized mice. The mAbs also exert direct antitumor effects. These results suggest that activation of innate immunity via disruption of HLA/LILR interactions is a potent approach for control of both primary tumors and potentially tumor metastases.

PubMed: 41032026
DOI: 10.1158/2326-6066.CIR-25-0343

Experimental method

X-RAY DIFFRACTION (2.3 Å)