Cross-species reactivity of the anti-idiotype anti-OKT3 cascade between mice and humans

The administration of murine mAb specific for the CD3ϵ 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 CD3ϵ chain. The M-12 mAb inhibited OKT3-induced mitogenesis and blocked (≈60%) the binding of OKT3 to peripheral blood (PBL) T-cell CD3ϵ chain in flow cytometry. In contrast, the G-880 mAb did not inhibit mitogenesis and only weakly blocked OKT3 binding to CD3ϵ chain (≈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 CD3ϵ 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 Ab2β and G-880 that of an Ab2α. 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.