7KQL
Anti-Tim3 antibody Fab complex
Summary for 7KQL
| Entry DOI | 10.2210/pdb7kql/pdb |
| Descriptor | Tim3.18 Fab heavy chain, Tim3.18 Fab light chain, Hepatitis A virus cellular receptor 2, ... (5 entities in total) |
| Functional Keywords | tim3 havcr2 fab antibody, immune system |
| Biological source | Homo sapiens More |
| Total number of polymer chains | 3 |
| Total formula weight | 63236.56 |
| Authors | Deng, X.A.,West, S.M.,Strop, P. (deposition date: 2020-11-16, release date: 2022-02-09, Last modification date: 2024-11-20) |
| Primary citation | Pagliano, O.,Morrison, R.M.,Chauvin, J.M.,Banerjee, H.,Davar, D.,Ding, Q.,Tanegashima, T.,Gao, W.,Chakka, S.R.,DeBlasio, R.,Lowin, A.,Kara, K.,Ka, M.,Zidi, B.,Amin, R.,Raphael, I.,Zhang, S.,Watkins, S.C.,Sander, C.,Kirkwood, J.M.,Bosenberg, M.,Anderson, A.C.,Kuchroo, V.K.,Kane, L.P.,Korman, A.J.,Rajpal, A.,West, S.M.,Han, M.,Bee, C.,Deng, X.,Schebye, X.M.,Strop, P.,Zarour, H.M. Tim-3 mediates T cell trogocytosis to limit antitumor immunity. J.Clin.Invest., 132:-, 2022 Cited by PubMed Abstract: T cell immunoglobulin mucin domain-containing protein 3 (Tim-3) negatively regulates innate and adaptive immunity in cancer. To identify the mechanisms of Tim-3 in cancer immunity, we evaluated the effects of Tim-3 blockade in human and mouse melanoma. Here, we show that human programmed cell death 1-positive (PD-1+) Tim-3+CD8+ tumor-infiltrating lymphocytes (TILs) upregulate phosphatidylserine (PS), a receptor for Tim-3, and acquire cell surface myeloid markers from antigen-presenting cells (APCs) through transfer of membrane fragments called trogocytosis. Tim-3 blockade acted on Tim-3+ APCs in a PS-dependent fashion to disrupt the trogocytosis of activated tumor antigen-specific CD8+ T cells and PD-1+Tim-3+ CD8+ TILs isolated from patients with melanoma. Tim-3 and PD-1 blockades cooperated to disrupt trogocytosis of CD8+ TILs in 2 melanoma mouse models, decreasing tumor burden and prolonging survival. Deleting Tim-3 in dendritic cells but not in CD8+ T cells impeded the trogocytosis of CD8+ TILs in vivo. Trogocytosed CD8+ T cells presented tumor peptide-major histocompatibility complexes and became the target of fratricide T cell killing, which was reversed by Tim-3 blockade. Our findings have uncovered a mechanism Tim-3 uses to limit antitumor immunity. PubMed: 35316223DOI: 10.1172/JCI152864 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.49 Å) |
Structure validation
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