Disclosed herein are the methods of using the H4-1BB protein, ligands to
this protein, and various mAbs either directed against H4-1BB or other molecules
that can be used therapeutically. The nature and importance of the H4-1BB molecule
provides the ligands and related co-stimulatory molecules the ability to enhance
or suppress T-cell activation and proliferation. By treating T-cells that have
expressed receptor protein H4-1BB with one of the four anti-H4-1BB monoclonal antibodies
disclosed herein activation or inhibition of the immune response is seen. Also
disclosed herein is cDNA for the human receptor H4-1BB. The cDNA of the human receptor
H4-1BB is about 65% homologous to the mouse cDNA 4-1BB and was isolated by using
probes derived from murine cDNA 4-1BB. A fusion protein for detecting cell membrane
ligands to human receptor protein H4-1BB was developed. It comprises the extracellular
portion of the receptor protein H4-1BB and a detection protein, alkaline phosphatase,
bound to the portion of the receptor protein H4-1BB. B-cells that have expressed
a ligand to receptor protein H4-1BB can be treated with cells that have expressed
receptor protein H4-1BB and B-cell proliferation may be induced. The use of H4-1BB
to block H4-1BB ligand binding has practical application in the suppression of
the immune system during organ transplantation or against autoimmune diseases including
diabetes, rheumatoid arthritis, and lupus. Other applications of this technology
include the development of therapeutic methods for the treatment of HIV-1 infected
individuals, and the treatment of cancerous tumors.
