Abstract
Lymphocyte activation gene-3 (LAG-3; CD223) is a CD4-related transmembrane protein that binds to MHC class II molecules. We have recently shown that LAG-3 is required for maximal regulatory T cell function, and that ectopic expression of LAG-3 is sufficient to confer regulatory activity. In this study we show that LAG-3 is cleaved within the D4 transmembrane domain connecting peptide into two fragments that remain membrane associated: a 54-kDa fragment that contains all the extracellular domains and oligomerizes with full-length LAG-3 (70 kDa) on the cell surface via the D1 domain, and a 16-kDa peptide that contains the transmembrane and cytoplasmic domains. This NH(2)-terminal fragment is subsequently released as soluble LAG-3 (sLAG-3), a process that is increased after T cell activation in vitro and in vivo, and is found in the sera of C57BL/6 and RAG-1(-/-) mice. Modulation of LAG-3 cleavage may contribute to the function of this key regulatory T cell protein.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antigens, CD / biosynthesis
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Antigens, CD / blood
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Antigens, CD / chemistry*
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Antigens, CD / genetics
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CD4-Positive T-Lymphocytes / chemistry*
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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Cell Line
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Cell Membrane / chemistry
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Cell Membrane / metabolism
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Humans
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Hybridomas
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Hydrolysis
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Lymphocyte Activation Gene 3 Protein
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Lymphocyte Activation* / genetics
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Membrane Proteins / biosynthesis
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Membrane Proteins / blood
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Molecular Sequence Data
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Peptide Fragments / biosynthesis
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Peptide Fragments / chemistry
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Peptide Fragments / metabolism
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Protein Structure, Tertiary
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Spleen / chemistry
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Spleen / cytology
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Spleen / immunology
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Spleen / metabolism
Substances
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Antigens, CD
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Membrane Proteins
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Peptide Fragments
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Lymphocyte Activation Gene 3 Protein