Synthesis and functional characterization of a recombinant monoclonal antibody directed against the alpha-chain of the human interleukin-2 receptor.
We have determined the sequence of the light and heavy chains of mAb 3G-10 (IgG1), a monoclonal antibody competing with interleukin 2 (IL2) for binding to the human IL2 receptor Tac protein. The antibody-encoding genes were chimerized by introducing splice donor and part of the intron sequences into the cDNA and subsequently linking it to the constant parts of the human IgG1 gene. The chimeric mAb was produced in mouse myeloma cells and purified. Murine and chimeric mAbs showed similar properties with respect to inhibition of T-cell proliferation. In contrast to its murine counterpart, the chimeric mAb exhibited Ab-dependent cellular cytotoxicity and, when combined with an Ab recognizing a different epitope on the IL2 receptor Tac protein, was able to activate human complement. The chimerized mAb might therefore have improved therapeutic efficacy.
Kaluza
B
B
Abteilung für DNS-Neukombination, Boehringer Mannheim GmbH, Penzberg, F.R.G.
Lenz
H
H
Russmann
E
E
Hock
H
H
Rentrop
O
O
Majdic
O
O
Knapp
W
W
Weidle
U H
UH
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D003001:Cloning, Molecular; D003167:Complement Activation; D003602:Cytotoxicity, Immunologic; D004558:Electric Stimulation; D005434:Flow Cytometry; D006801:Humans; D006825:Hybridomas; D007074:Immunoglobulin G / Q000235:genetics; D007438:Introns / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins