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

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

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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Crossref · 10.4049/jimmunol.169.10.5392

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  • A single lysine residue (Lys468) within the KIEELE motif exerts an inhibitory effect in CD4+ T lymphocytes.

    “Notably, a single lysine residue (Lys468) exerts an inhibitory effect in CD4+ T lymphocytes at 468 motifs within the KIEELE [324].”

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Authors
Workman, C. J., Dugger, K. J., & Vignali, D. A. A.
Affiliations
St. Jude Children's Research Hospital (US)
Venue
The Journal of Immunology
Published
2002-11
Volume
169
Issue
10
Pages
5392-5395
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
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
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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