Inducible T cell antigen 4-1BB. Analysis of expression and function.
4-1BB is an inducible receptor-like protein expressed in both cytolytic and Th cells. Optimal induction of 4-1BB mRNA in T cells required both PMA and ionomycin stimulation, indicating that protein kinase C activation and increases in intracellular Ca2+ were required for its expression. 4-1BB was categorized as an early activation gene since the protein synthesis inhibitor, cycloheximide, blocked the induction of 4-1BB mRNA. A rat mAb, 53A2, was generated against recombinant soluble 4-1BB and was used to characterize this molecule. 4-1BB is a 30-kDa glycoprotein and appears to exist as both a monomer and a 55-kDa dimer on the cell surface of a T cell clone. The 4-1BB protein may be post-translationally modified since its predicted backbone is 25 kDa. FACS analysis indicated that 4-1BB was inducible and expressed on the cell surface of activated splenic T cells and thymocytes. Cross-linking of 4-1BB on anti-CD3-stimulated T cells with 53A2 resulted in a dramatic enhancement of T cell proliferation. This suggests that 4-1BB may function as an accessory signaling molecule during T cell activation.
Pollok
K E
KE
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis 46202.
Kim
Y J
YJ
Zhou
Z
Z
Hurtado
J
J
Kim
K K
KK
Pickard
R T
RT
Kwon
B S
BS
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D001483:Base Sequence; D019013:CD40 Antigens; D005260:Female; D007106:Immune Sera / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000032:analysis* / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D007106:Immune Sera; D011948:Receptors, Antigen, T-Cell