7ZUC

Human Major Histocompatibility Complex A2 allele presenting LLLGIGILV

7ZUC の概要

• エントリーDOI: 10.2210/pdb7zuc/pdb
• 分子名称: MHC class I antigen, Beta-2-microglobulin, LEU-LEU-LEU-GLY-ILE-GLY-ILE-LEU-VAL, ... (5 entities in total)
• 機能のキーワード: human, mhc, melanoma, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 89854.14

構造登録者

Rizkallah, P.J.,Wall, A.,Sewell, A.K.,Fuller, A. (登録日: 2022-05-12, 公開日: 2023-05-24, 最終更新日: 2024-11-06)

主引用文献

Dolton, G.,Rius, C.,Wall, A.,Szomolay, B.,Bianchi, V.,Galloway, S.A.E.,Hasan, M.S.,Morin, T.,Caillaud, M.E.,Thomas, H.L.,Theaker, S.,Tan, L.R.,Fuller, A.,Topley, K.,Legut, M.,Attaf, M.,Hopkins, J.R.,Behiry, E.,Zabkiewicz, J.,Alvares, C.,Lloyd, A.,Rogers, A.,Henley, P.,Fegan, C.,Ottmann, O.,Man, S.,Crowther, M.D.,Donia, M.,Svane, I.M.,Cole, D.K.,Brown, P.E.,Rizkallah, P.,Sewell, A.K.
Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy.
Cell, 186:3333-3349.e27, 2023

PubMed Abstract: The T cells of the immune system can target tumors and clear solid cancers following tumor-infiltrating lymphocyte (TIL) therapy. We used combinatorial peptide libraries and a proteomic database to reveal the antigen specificities of persistent cancer-specific T cell receptors (TCRs) following successful TIL therapy for stage IV malignant melanoma. Remarkably, individual TCRs could target multiple different tumor types via the HLA A02:01-restricted epitopes EAAGIGILTV, LLLGIGILVL, and NLSALGIFST from Melan A, BST2, and IMP2, respectively. Atomic structures of a TCR bound to all three antigens revealed the importance of the shared x-x-x-A/G-I/L-G-I-x-x-x recognition motif. Multi-epitope targeting allows individual T cells to attack cancer in several ways simultaneously. Such "multipronged" T cells exhibited superior recognition of cancer cells compared with conventional T cell recognition of individual epitopes, making them attractive candidates for the development of future immunotherapies.

PubMed: 37490916
DOI: 10.1016/j.cell.2023.06.020

実験手法

X-RAY DIFFRACTION (1.89 Å)