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PMID:12421911
| Citation |
Workman, CJ, Dugger, KJ and Vignali, DA (2002) Cutting edge: molecular analysis of the negative regulatory function of lymphocyte activation gene-3. J. Immunol. 169:5392-5 |
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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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| Keywords |
Amino Acid Motifs; Amino Acid Sequence; Animals; Antigens, CD; Antigens, CD4/physiology; Conserved Sequence; Cytoplasm/immunology; Down-Regulation/immunology; Histocompatibility Antigens Class II/immunology; Histocompatibility Antigens Class II/metabolism; Humans; Hybridomas; Ligands; Lymphocyte Activation/immunology; Membrane Proteins/chemistry; Membrane Proteins/immunology; Membrane Proteins/metabolism; Membrane Proteins/physiology; Mice; Molecular Sequence Data; Protein Structure, Tertiary; Tumor Cells, Cultured |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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