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

Manuel Carreno, Laphalle Fuller, Keith Zucker, Wen Chic Yang, George W Burke, Jose Nery, Carmen Gomez, Violet Esquenazi, Joshua Miller

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Abstract

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

Original languageEnglish
Pages (from-to)249-258
Number of pages10
JournalHuman Immunology
Volume33
Issue number4
DOIs
StatePublished - Jan 1 1992

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Muromonab-CD3
T-Lymphocytes
Anti-Idiotypic Antibodies
Blood Cells
Immunoglobulin G

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Cross-species reactivity of the anti-idiotype anti-OKT3 cascade between mice and humans. / Carreno, Manuel; Fuller, Laphalle; Zucker, Keith; Yang, Wen Chic; Burke, George W; Nery, Jose; Gomez, Carmen; Esquenazi, Violet; Miller, Joshua.

In: Human Immunology, Vol. 33, No. 4, 01.01.1992, p. 249-258.

Research output: Contribution to journalArticle

Carreno, M, Fuller, L, Zucker, K, Yang, WC, Burke, GW, Nery, J, Gomez, C, Esquenazi, V & Miller, J 1992, 'Cross-species reactivity of the anti-idiotype anti-OKT3 cascade between mice and humans', Human Immunology, vol. 33, no. 4, pp. 249-258. https://doi.org/10.1016/0198-8859(92)90332-H
Carreno, Manuel ; Fuller, Laphalle ; Zucker, Keith ; Yang, Wen Chic ; Burke, George W ; Nery, Jose ; Gomez, Carmen ; Esquenazi, Violet ; Miller, Joshua. / Cross-species reactivity of the anti-idiotype anti-OKT3 cascade between mice and humans. In: Human Immunology. 1992 ; Vol. 33, No. 4. pp. 249-258.
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abstract = "The administration of murine mAb specific for the CD3ε{lunate} 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{lunate} chain. The M-12 mAb inhibited OKT3-induced mitogenesis and blocked (≈60{\%}) the binding of OKT3 to peripheral blood (PBL) T-cell CD3ε{lunate} chain in flow cytometry. In contrast, the G-880 mAb did not inhibit mitogenesis and only weakly blocked OKT3 binding to CD3ε{lunate} 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{lunate} 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.",
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