Biochemical analysis of the regulatory T cell protein lymphocyte activation gene-3 (LAG-3; CD223).
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.
Li
Nianyu
N
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Workman
Creg J
CJ
Martin
Stefani M
SM
Vignali
Dario A A
DA
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000097:blood / Q000737:chemistry* / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006825:Hybridomas; D006868:Hydrolysis; D008213:Lymphocyte Activation / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000097:blood / Q000737:chemistry / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013154:Spleen / Q000737:chemistry / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000093322:Lymphocyte Activation Gene 3 Protein
D015703:Antigens, CD; D008565:Membrane Proteins; D010446:Peptide Fragments; D000093322:Lymphocyte Activation Gene 3 Protein