MOUSE LYMPHOTOXIN-BETA RECEPTOR - MOLECULAR-GENETICS, LIGAND-BINDING,AND EXPRESSION

Lymphotoxin (LT)-alpha beta heterotrimer is a membrane-anchored ligand expressed by activated T cells which binds specifically to the LT bet a receptor (LT beta R), a member of the TN beta R family. The LT beta R is implicated as a critical element in controlling lymph node develo pment and cellular immune reactions. To address this hypothesis we hav e isolated a mouse cDNA encoding a single transmembrane protein of 415 amino acids with 76% identity to human LT beta R. The receptor functi on of this molecule was demonstrated by the ability of the extracellul ar domain, constructed as a chimera with the Fc region of IgG1, to bin d to LT alpha beta complexes expressed on the surface of activated T c ells or insect cells infected with baculoviruses containing LT alpha a nd 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 closel y linked to Tnfr1, consistent with the tight linkage of the human homo logue of these genes on chromosome 12p13. Mouse LT beta R mRNA is expr essed by cell lines of monocytic and epithelial origin but not by a CT L line, and in vivo it is constitutively expressed in visceral and lym phoid tissues. The delineation of the structure of the mouse LT beta R will aid investigations into the role of this cytokine-receptor syste m in immune function and development.