title: Cross-species reactivity of the anti-idiotype anti-OKT3 cascade between mice and humans.
abstract: The administration of murine mAb specific for the CD3 epsilon subunit of the TCR complex (OKT3) has been demonstrated to engender in humans an anti-OKT3 idiotypic cascade. This study used murine-derived anti-OKT3 (Ab2) as a bioreagent to determine whether this Ab2 and polyclonal anti-(anti-OKT3) (Ab3) generated in some human kidney transplant patients are idiotypically connected. Two anti-OKT3 mAbs G-880 (IgG1) and M-12 (IgM) were derived by immunizing BALB/c mice with the OKT3-secreting hybridoma. The two mAbs exhibited specificity for OKT3 F(ab)'2 idiotypic determinants. Both mAbs were tested for their ability to inhibit OKT3 induced mitogenesis and to block FITC-OKT3 binding to cell surface CD3 epsilon chain. The M-12 mAb inhibited OKT3-induced mitogenesis and blocked (approximately 60%) the binding of OKT3 to peripheral blood (PBL) T-cell CD3 epsilon chain in flow cytometry. In contrast, the G-880 mAb did not inhibit mitogenesis and only weakly blocked OKT3 binding to CD3 epsilon chain (approximately 12%). Sera of kidney transplant recipients who received OKT3 antirejection therapy and who developed antiidiotypic anti-OKT3 antibodies could be divided into two subgroups exhibiting anti-OKT3 activity: (a) those who had similar specificity as M-12 and failed to enhance the M-12 inhibition of OKT3 binding to PBL T-cell CD3 epsilon chain when added as a third component (n = 3), and (b) those with anti-OKT3 antibodies with idiotype specificity dissimilar to M-12 and who were able to increase the (maximum 60%) inhibition obtained with M-12 in the OKT3 to T-cell CD3-binding assay (n = 4). From these observations, we conclude that M-12 had the characteristics of an Ab2 beta and G-880 that of an Ab2 alpha. Additionally, there was an idiotypic connectivity of mouse-derived M-12 anti-OKT3 (Ab2) and OKT3-engendered human polyclonal anti-(anti-OKT3) (Ab3), in that three of seven patients examined had human serum IgG antibodies that specifically recognized M-12 idiotypic determinants as demonstrated in ELISA.
authors.affiliation: Department of Surgery, University of Miami School of Medicine, FL 33136.
authors.forename: M
authors.initials: M
authors.lastname: Carreno
authors.forename: L
authors.initials: L
authors.lastname: Fuller
authors.forename: K
authors.initials: K
authors.lastname: Zucker
authors.forename: W C
authors.initials: WC
authors.lastname: Yang
authors.forename: G
authors.initials: G
authors.lastname: Burke
authors.forename: J
authors.initials: J
authors.lastname: Nery
authors.forename: C
authors.initials: C
authors.lastname: Gomez
authors.forename: V
authors.initials: V
authors.lastname: Esquenazi
authors.forename: J
authors.initials: J
authors.lastname: Miller
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D017252:CD3 Complex; D003429:Cross Reactions / Q000235:genetics*; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016853:Muromonab-CD3 / Q000276:immunology* / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016853:Muromonab-CD3; D011948:Receptors, Antigen, T-Cell