8TQ5

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

8TQ5 の概要

• エントリーDOI: 10.2210/pdb8tq5/pdb
• 関連するPDBエントリー: 8TQ4 8TQ6 8TQ7 8TQ8 8TQ9 8TQA
• 分子名称: HLA class I histocompatibility antigen B alpha chain (HLA-B*44:05), Beta-2-microglobulin, MHC class II antigen, ... (7 entities in total)
• 機能のキーワード: histocompatibility complex class i, mhc-i, immune response, immune system fab, antibody, anti-mhc antibody, cancer tumor, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 92465.79

構造登録者

Jiang, J.,Natarajan, K.,Boyd, L.F.,Margulies, D.H. (登録日: 2023-08-06, 公開日: 2025-02-05, 最終更新日: 2025-10-08)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.3 Å)