Inducible T cell antigen 4-1BB. Analysis of expression and function

• Published in: The Journal of immunology (1950) Vol. 150; no. 3; pp. 771 - 781
• Main Authors: Pollok, KE, Kim, YJ, Zhou, Z, Hurtado, J, Kim, KK, Pickard, RT, Kwon, BS
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01.02.1993; American Association of Immunologists
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal - immunology; Antigens, CD - physiology; Antigens, Differentiation, B-Lymphocyte - physiology; Base Sequence; Biological and medical sciences; CD40 Antigens; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immune Sera - immunology; Immunobiology; Lymphocyte Activation; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Receptors, Antigen, T-Cell - analysis; Receptors, Antigen, T-Cell - immunology; Receptors, Antigen, T-Cell - physiology; T-Lymphocytes - immunology; Flow cytometry; Rat; Thymocyte; Rodentia; Biological marker; Activation; Glycoproteins; Splenocyte; Posttranslational modification; Signal transduction; Vertebrata; Mammalia; Messenger RNA; T-Lymphocyte; Dimer
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.150.3.771

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.