Combinatorial functions of two chimeric antibodies directed to human CD4 and one directed to the alpha-chain of the human interleukin-2 receptor.
The general feasibility of chimerization of monoclonal antibodies (mAbs) has already been shown for a large number of them. In order to evaluate in vitro parameters relevant to immunosuppressive therapy, we have chimerized and synthesized two anti-CD4 mAbs recognizing two different epitopes on the human T-lymphocyte antigen, CD4. The chimerized mAbs are produced at levels corresponding to those of the original hybridoma cell lines. With respect to activation of human complement, the individual Abs are negative; however, when used in combination, complement activation was performed. When applied in combination, they were found to modulate the CD4 antigen, whereas the individual mAb do not display this property. Individually they mediate an up to 60% inhibition of the mixed lymphocyte reaction (MLR). However, by combination of an anti-CD4 mAb with one directed against the alpha-chain of the human IL2 receptor, nearly 100% inhibition of the MLR was achieved, even with reduced dosage of the mAbs. Our data suggest that the combination of an anti-CD4 mAb and an anti-IL2R alpha chain mAb is more effective with respect to immunosuppression than each mAb by itself, indicating that this mAb cocktail could be a new strategy for immunosuppressive therapy.
Weissenhorn
W
W
Institut für Immunologie, Universität München, Munich, Germany.
Scheuer
W
W
Kaluza
B
B
Schwirzke
M
M
Reiter
C
C
Flieger
D
D
Lenz
H
H
Weiss
E H
EH
Rieber
E P
EP
Riethmüller
G
G
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000737:chemistry*; D000937:Antigen-Antibody Reactions; D016525:Antigenic Modulation; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology*; D003001:Cloning, Molecular; D003167:Complement Activation; D015870:Gene Expression; D006801:Humans; D006825:Hybridomas; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D011993:Recombinant Fusion Proteins; D014162:Transfection
D000906:Antibodies; D015704:CD4 Antigens; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins