7ZUC

Human Major Histocompatibility Complex A2 allele presenting LLLGIGILV

Summary for 7ZUC

• Entry DOI: 10.2210/pdb7zuc/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, LEU-LEU-LEU-GLY-ILE-GLY-ILE-LEU-VAL, ... (5 entities in total)
• Functional Keywords: human, mhc, melanoma, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 89854.14

Authors

Rizkallah, P.J.,Wall, A.,Sewell, A.K.,Fuller, A. (deposition date: 2022-05-12, release date: 2023-05-24, Last modification date: 2024-02-07)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.89 Å)