Depletion of bovine CD8+ T cells with chCC63, a chimaeric mouse-bovine antibody.
In order to investigate the role of T cells in immune responses to infectious pathogens, depletion of individual T cell subsets using monoclonal antibodies (mAbs) is commonly undertaken. Since most mAbs are of murine origin, such depletion studies in cattle are restricted by the bovine anti-mouse antibody (BAMA) response to the mouse mAbs used for the depletions. In this study, we describe the use of antibody engineering to overcome the BAMA response. The variable region cDNA from CC63, a monoclonal mouse anti-bovine CD8 antibody, has been expressed in conjunction with bovine constant region genes to produce a mouse-bovine chimaeric antibody (chCC63). Characterisation of chCC63 showed that the antibody contained a bovine constant region and specifically bound bovine CD8+ T cells. Furthermore, chCC63 blocked the binding of the original mouse antibody, CC63, and mediated complement-dependent lysis of bovine CD8+ cells in vitro. In vivo, chCC63 depleted calves of CD8+ T cells as effectively as CC63 and provoked a BAMA response that was about one-tenth of that seen with the mouse antibody.
Bruce
C J
CJ
Institute for Animal Health, Compton, Newbury, Berks, UK.
Howard
C J
CJ
Thomas
L H
LH
Tempest
P R
PR
Taylor
G
G
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000911:Antibodies, Monoclonal / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002417:Cattle / Q000276:immunology*; D003165:Complement System Proteins / Q000502:physiology; D008212:Lymphocyte Depletion; D051379:Mice; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011993:Recombinant Fusion Proteins; D003165:Complement System Proteins