Mouse lymphotoxin-beta receptor. Molecular genetics, ligand binding, and expression
Force, W.R.; Walter, B.N.; Hession, C.; Tizard, R.; Kozak, C.A.; Browning, J.L.; Ware, C.F.
Journal of Immunology 155(11): 5280-5288
1995
ISSN/ISBN: 0022-1767 PMID: 7594541 Document Number: 445524
Lymphotoxin (LT) -alpha-beta heterotrimer is a membrane-anchored ligand expressed by activated T cells which binds specifically to the LT-beta receptor (LT-beta-R), a member of the TNFR family. The LT-beta-R is implicated as a critical element in controlling lymph node development and cellular immune reactions. To address this hypothesis we have isolated a mouse cDNA encoding a single transmembrane protein of 415 amino acids with 76% identity to human LT-beta-R. The receptor function of this molecule was demonstrated by the ability of the extracellular domain, constructed as a chimera with the Fc region of IgG1, to bind to LT-alpha-beta complexes expressed on the surface of activated T cells or insect cells infected with baculoviruses containing LT-alpha and LT-beta cDNAs. The gene encoding mouse LT-beta-R, Ltbr, contains 10 exons spanning 6.9 kb and maps to mouse chromosome 6, which is closely linked to Tnfr1, consistent with the tight linkage of the human homologue of these genes on chromosome 12p13. Mouse LT-beta-R mRNA is expressed by cell lines of monocytic and epithelial origin but not by a CTL line, and in vivo it is constitutively expressed in visceral and lymphoid tissues. The delineation of the structure of the mouse LT-beta-R will aid investigations into the role of this cytokine-receptor system in immune function and development.