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PMID: 2513570 Published · ppublish English Journal Article

A humanized antibody that binds to the interleukin 2 receptor.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 86 ·No. 24 ·1989-12-00 ·Pages 10029-33

Queen C, Schneider WP, Selick HE, Payne PW, Landolfi NF, Duncan JF, Avdalovic NM, Levitt M, Junghans RP, Waldmann TA

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Antibodies, Monoclonal/genetics,immunology Antigen-Antibody Complex Base Sequence Chimera Cloning, Molecular Computer Simulation Exons Genes, Immunoglobulin Humans Immunoglobulin Constant Regions/genetics Immunoglobulin Heavy Chains/genetics Immunoglobulin Light Chains/genetics Immunoglobulin Variable Region/genetics Mice Models, Molecular Molecular Sequence Data Oligonucleotide Probes Plasmids Protein Conformation Receptors, Interleukin-2/immunology Sequence Homology, Nucleic Acid Software
Chemicals
Antibodies, Monoclonal Antigen-Antibody Complex Immunoglobulin Constant Regions Immunoglobulin Heavy Chains Immunoglobulin Light Chains Immunoglobulin Variable Region Oligonucleotide Probes Receptors, Interleukin-2
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Queen C
Protein Design Labs, Palo Alto, CA 94304.
Schneider W P
Selick H E
Payne P W
Landolfi N F
Duncan J F
Avdalovic N M
Levitt M
Junghans R P
Waldmann T A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.86.24.10029
Published
1989-12-00
Pages
10029-33
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC298637
Subset
IM
Databases
GENBANK
M28250, M28251
External Links
PubMed source DOI: 10.1073/pnas.86.24.10029 PMC Full Text View journal details
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