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.
journal_name
Proc Natl Acad Sci U S Aauthors
Queen C,Schneider WP,Selick HE,Payne PW,Landolfi NF,Duncan JF,Avdalovic NM,Levitt M,Junghans RP,Waldmann TAdoi
10.1073/pnas.86.24.10029subject
Has Abstractpub_date
1989-12-01 00:00:00pages
10029-33issue
24eissn
0027-8424issn
1091-6490journal_volume
86pub_type
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