Cited by 390T-cell and B-cell ImmunologyCancer Immunotherapy and BiomarkersReproductive System and Pregnancy

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Cutting Edge: Molecular Analysis of the Negative Regulatory Function of Lymphocyte Activation Gene-3

Workman, Creg J, Dugger, Kari J, Vignali, Dario A A·2002·The Journal of Immunology

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Abstract

Lymphocyte activation gene (LAG)-3 (CD223) is a CD4-related activation-induced cell surface molecule that binds to MHC class II molecules with high affinity and negatively regulates T cell expansion and homeostasis. In this study, we show that LAG-3 inhibits CD4-dependent, but not CD4-independent, T cell function via its cytoplasmic domain. Although high affinity interaction with MHC class II molecules is essential for LAG-3 function, tailless LAG-3 does not compete with CD4 for ligand binding. A single lysine residue (K468) within a conserved "KIEELE" motif is essential for interaction with downstream signaling molecules. These data provide insight into the mechanism of action of this important T cell regulatory molecule.

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Authors: Workman, C. J., Dugger, K. J., & Vignali, D. A. A.
Affiliations: St. Jude Children's Research Hospital (US)
ORCID: Workman, Creg J
Dugger, Kari J
Vignali, Dario A A
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2002-11
Volume: 169
Issue: 10
Pages: 5392-5395
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.169.10.5392
OpenAlex: W1480698358
Cited by: 389
References: 26
Citations by year: 2026: 18 · 2025: 28 · 2024: 50 · 2023: 41 · 2022: 37 · 2021: 30 · 2020: 38 · 2019: 30 · 2018: 25 · 2017: 17 · 2016: 9 · 2015: 12 · 2014: 3 · 2013: 4 · 2012: 7
FWCI: 1.42
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (CA-09346, T32CA009346, CA23944, CA21765, R25CA023944, P30CA021765)
National Institute of Allergy and Infectious Diseases (T32AI007372, AI-07372, AI39480)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Keywords: LAG-3, T cell regulation, MHC class II binding, cytoplasmic domain, negative regulation of T cell activation
MeSH terms: Lymphocyte Activation Gene 3 Protein, Amino Acid Sequence, Animals, Histocompatibility Antigens Class II, Cytoplasm, Humans, Hybridomas, Ligands, Lymphocyte Activation, Membrane Proteins, Molecular Sequence Data, Tumor Cells, Cultured, Down-Regulation, Antigens, CD, CD4 Antigens, Conserved Sequence, Protein Structure, Tertiary, Amino Acid Motifs, Mice

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Cutting Edge: Molecular Analysis of the Negative Regulatory Function of Lymphocyte Activation Gene-3

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