Characterization of human homologue of 4-1BB and its ligand

Immunol Lett. 1995 Feb;45(1-2):67-73. doi: 10.1016/0165-2478(94)00227-i.


The human homologue of 4-1BB (H4-1BB) cDNA was isolated from PMA plus ionomycin-treated human peripheral T-cell cDNA libraries. The amino acid sequence deduced from the nucleotide sequence showed that the protein is composed of 255 amino acids with 2 potential N-linked glycosylation sites. The molecular weight of its protein backbone is calculated to be 27 kDa. The H4-1BB contains features such as signal sequence and transmembrane domain, indicating that it is a receptor protein. This protein showed 60% identity of amino acid sequence to mouse 4-1BB. In the cytoplasmic domain there are 5 regions of amino acid sequences conserved from mouse to human, indicating that these residues might be important in the 4-1BB function. H4-1BB mRNA was detected in unstimulated peripheral blood T cells and was inducible in T-cell lines such as Jurkat and CEM. H4-1BB-AP, a fusion protein between the H4-1BB extracellular domain and alkaline phosphatase, was used to identify the ligand for the H4-1BB. Although the H4-1BB ligand was detected in both T and B cells of human peripheral blood, the ligand was preferentially expressed in primary B cells and B-cell lines. Daudi, a B-cell lymphoma, was one of the B-cell lines that carried a higher number of ligands. Scatchard analysis showed that the Kd = 1.4 x 10(9) M and the number of ligands in Daudi cell was 4.2 x 10(3).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • 4-1BB Ligand
  • Amino Acid Sequence
  • Animals
  • Antigens, CD
  • B-Lymphocytes / metabolism
  • Base Sequence
  • DNA, Complementary / genetics
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / pathology
  • Lymphocyte Activation
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / isolation & purification
  • Mice
  • Molecular Sequence Data
  • Molecular Weight
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Polymerase Chain Reaction
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Protein Structure, Tertiary
  • RNA, Messenger / analysis
  • Receptors, Nerve Growth Factor / chemistry*
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / isolation & purification
  • Receptors, Tumor Necrosis Factor / chemistry*
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / isolation & purification
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Species Specificity
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Tumor Necrosis Factor-alpha / chemistry*


  • 4-1BB Ligand
  • Antigens, CD
  • DNA, Complementary
  • Membrane Glycoproteins
  • Peptide Fragments
  • RNA, Messenger
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • Recombinant Fusion Proteins
  • TNFRSF9 protein, human
  • TNFSF9 protein, human
  • Tnfrsf9 protein, mouse
  • Tnfsf9 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Tumor Necrosis Factor-alpha