A humanized antibody that binds to the interleukin 2 receptor.
The anti-Tac monoclonal antibody is known to bind to the p55 chain of the human interleukin 2 receptor and to inhibit proliferation of T cells by blocking interleukin 2 binding. However, use of anti-Tac as an immunosuppressant drug would be impaired by the human immune response against this murine antibody. We have therefore constructed a "humanized" antibody by combining the complementarity-determining regions (CDRs) of the anti-Tac antibody with human framework and constant regions. The human framework regions were chosen to maximize homology with the anti-Tac antibody sequence. In addition, a computer model of murine anti-Tac was used to identify several amino acids which, while outside the CDRs, are likely to interact with the CDRs or antigen. These mouse amino acids were also retained in the humanized antibody. The humanized anti-Tac antibody has an affinity for p55 of 3 x 10(9) M-1, about 1/3 that of murine anti-Tac.
Queen
C
C
Protein Design Labs, Palo Alto, CA 94304.
Schneider
W P
WP
Selick
H E
HE
Payne
P W
PW
Landolfi
N F
NF
Duncan
J F
JF
Avdalovic
N M
NM
Levitt
M
M
Junghans
R P
RP
Waldmann
T A
TA
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D000936:Antigen-Antibody Complex; D001483:Base Sequence; D002678:Chimera; D003001:Cloning, Molecular; D003198:Computer Simulation; D005091:Exons; D005803:Genes, Immunoglobulin; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010957:Plasmids; D011487:Protein Conformation; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D012689:Sequence Homology, Nucleic Acid; D012984:Software
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D015345:Oligonucleotide Probes; D015375:Receptors, Interleukin-2