دورية أكاديمية
Cutting Edge: LAG3 Dimerization Is Required for TCR/CD3 Interaction and Inhibition of Antitumor Immunity.
| العنوان: | Cutting Edge: LAG3 Dimerization Is Required for TCR/CD3 Interaction and Inhibition of Antitumor Immunity. |
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| المؤلفون: | Adam K; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA.; Tumor Microenvironment Center, University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA., Lipatova Z; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA.; Tumor Microenvironment Center, University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA., Abdul Ghafoor Raja M; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA.; Tumor Microenvironment Center, University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA., Mishra AK; W. M. Keck Laboratory for Structural Biology, University of Maryland Institute for Biosciences and Biotechnology Research, Rockville, MD.; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD., Mariuzza RA; W. M. Keck Laboratory for Structural Biology, University of Maryland Institute for Biosciences and Biotechnology Research, Rockville, MD.; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD., Workman CJ; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA.; Tumor Microenvironment Center, University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA., Vignali DAA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA.; Tumor Microenvironment Center, University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA.; Cancer Immunology and Immunotherapy Program, University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA. |
| المصدر: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2024 Jul 01; Vol. 213 (1), pp. 7-13. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Bethesda, MD : American Association of Immunologists Original Publication: Baltimore : Williams & Wilkins, c1950- |
| مواضيع طبية MeSH: | Lymphocyte Activation Gene 3 Protein* , Antigens, CD*/immunology , Antigens, CD*/metabolism , Antigens, CD*/genetics , Protein Multimerization* , CD8-Positive T-Lymphocytes*/immunology, Animals ; Mice ; Melanoma, Experimental/immunology ; Mice, Inbred C57BL ; Receptor-CD3 Complex, Antigen, T-Cell/immunology ; CD3 Complex/immunology ; Humans ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/metabolism ; Lymphocyte Activation/immunology ; Protein Binding |
| مستخلص: | Lymphocyte activation gene 3 (LAG3) is an inhibitory receptor that plays a critical role in controlling T cell tolerance and autoimmunity and is a major immunotherapeutic target. LAG3 is expressed on the cell surface as a homodimer but the functional relevance of this is unknown. In this study, we show that the association between the TCR/CD3 complex and a murine LAG3 mutant that cannot dimerize is perturbed in CD8+ T cells. We also show that LAG3 dimerization is required for optimal inhibitory function in a B16-gp100 tumor model. Finally, we demonstrate that a therapeutic LAG3 Ab, C9B7W, which does not block LAG3 interaction with its cognate ligand MHC class II, disrupts LAG3 dimerization and its association with the TCR/CD3 complex. These studies highlight the functional importance of LAG3 dimerization and offer additional approaches to therapeutically target LAG3. (Copyright © 2024 by The American Association of Immunologists, Inc.) |
| التعليقات: | Erratum in: J Immunol. 2024 Aug 19:ji2400421. doi: 10.4049/jimmunol.2400421. (PMID: 39158271) |
| References: | Sci Rep. 2017 Feb 02;7:41351. (PMID: 28150718) J Exp Med. 2021 Jan 4;218(1):. (PMID: 33045061) Immunity. 2004 Oct;21(4):503-13. (PMID: 15485628) Nat Biotechnol. 2008 Feb;26(2):235-40. (PMID: 18157118) Clin Cancer Res. 2022 Dec 1;28(23):5030-5039. (PMID: 35579997) Structure. 2023 Oct 5;31(10):1149-1157.e3. (PMID: 37619561) J Immunol. 2004 Dec 1;173(11):6806-12. (PMID: 15557174) J Biol Chem. 2019 Apr 12;294(15):6017-6026. (PMID: 30760527) Cancer Res. 2012 Feb 15;72(4):917-27. (PMID: 22186141) J Immunol. 2022 Oct 15;209(8):1586-1594. (PMID: 36104110) Eur J Immunol. 2002 Aug;32(8):2255-63. (PMID: 12209638) N Engl J Med. 2022 Jan 6;386(1):24-34. (PMID: 34986285) J Immunol. 2011 Oct 1;187(7):3493-8. (PMID: 21873518) J Mol Biol. 2013 Nov 15;425(22):4595-613. (PMID: 23978698) Sci Immunol. 2020 Jul 17;5(49):. (PMID: 32680952) Immunity. 2022 May 10;55(5):912-924.e8. (PMID: 35413245) Immunol Rev. 2017 Mar;276(1):80-96. (PMID: 28258692) Sci Immunol. 2017 Mar 31;2(9):. (PMID: 28783703) Proc Natl Acad Sci U S A. 2021 Feb 9;118(6):. (PMID: 33526682) Eur J Immunol. 1996 May;26(5):1180-6. (PMID: 8647185) Nat Immunol. 2022 Jul;23(7):1031-1041. (PMID: 35761082) Proc Natl Acad Sci U S A. 2024 Mar 19;121(12):e2310866121. (PMID: 38483996) Science. 1996 Apr 19;272(5260):405-8. (PMID: 8602528) Nat Immunol. 2022 May;23(5):757-767. (PMID: 35437325) Protein Sci. 1994 May;3(5):717-29. (PMID: 8061602) Nat Protoc. 2017 Sep;12(9):1980-1998. (PMID: 28858287) Eur J Immunol. 2010 Jun;40(6):1768-77. (PMID: 20391435) Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):1989-94. (PMID: 20080695) Cell. 2019 Jan 10;176(1-2):334-347.e12. (PMID: 30580966) Nat Immunol. 2023 Sep;24(9):1415-1422. (PMID: 37488429) |
| معلومات مُعتمدة: | P01 AI108545 United States AI NIAID NIH HHS; R01 AI144422 United States AI NIAID NIH HHS |
| المشرفين على المادة: | 0 (Lymphocyte Activation Gene 3 Protein) 0 (Antigens, CD) 0 (Lag3 protein, mouse) 0 (Receptor-CD3 Complex, Antigen, T-Cell) 0 (CD3 Complex) 0 (Receptors, Antigen, T-Cell) |
| تواريخ الأحداث: | Date Created: 20240522 Date Completed: 20240617 Latest Revision: 20240819 |
| رمز التحديث: | 20240819 |
| مُعرف محوري في PubMed: | PMC11182711 |
| DOI: | 10.4049/jimmunol.2300673 |
| PMID: | 38775415 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1550-6606 |
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| DOI: | 10.4049/jimmunol.2300673 |