A humanized CD18 antibody can block function without cell destruction.
Leukocyte integrins are intimately involved in transient adherence of leukocytes to endothelium and to each other in the processes of extravasation and cell activation. In this study, seven mAb directed against human CD11a and two mAb directed against human CD18, the alpha- and beta-chains of the leukocyte functional Ag-1 molecule, respectively, were analyzed for their ability to inhibit several leukocyte functional Ag-1-mediated interactions. The best blocking mAb in these studies, a rat anti-human CD18, YFC51.1, was subsequently humanized by complementarily-determining region grafting, associated with human C regions and expressed. The humanized mAb was shown to maintain binding for human CD18. Even though the humanized mAb was an IgG1 isotype it still retained the functional blocking characteristics of the rat mAb while failing to mediate cell killing. The IgG1 mAb was unable to bind human Clq and could block but did not mediate antibody-dependent cellular cytotoxicity.
Sims
M J
MJ
Department of Cell Biology, Wellcome Research Laboratories, Beckenham, United Kingdom.
Hassal
D G
DG
Brett
S
S
Rowan
W
W
Lockyer
M J
MJ
Angel
A
A
Lewis
A P
AP
Hale
G
G
Waldmann
H
H
Crowe
J S
JS
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D000937:Antigen-Antibody Reactions; D015703:Antigens, CD / Q000276:immunology*; D001483:Base Sequence; D018821:CD18 Antigens; D002448:Cell Adhesion; D002449:Cell Aggregation / Q000187:drug effects; D002478:Cells, Cultured; D015922:Complement C1q / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000276:immunology; D000939:Epitopes; D006801:Humans; D066298:In Vitro Techniques; D007518:Isoantibodies / Q000276:immunology*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013045:Species Specificity
D015703:Antigens, CD; D018821:CD18 Antigens; D000939:Epitopes; D007518:Isoantibodies; D016169:Lymphocyte Function-Associated Antigen-1; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D015922:Complement C1q