SEARCH

SEARCH BY CITATION

Keywords:

  • Immunotoxin;
  • T cell receptor;
  • Vβ;
  • Toxicity

Abstract

The potency and specificity of anti-T cell receptor (TcR)-directed immunotoxins were studied in two T cell leukemia lines, HPB-ALL and Jurkat, and in primary T cells. Immunoconjugates were synthesized using anti-CD3ϵ or distinct anti-Vβ antibodies cross-linked to CRM9, a binding site-mutant of diphtheria toxin. All TcR-expressing cells display the CD3 complex on the plasma membrane. HPB-ALL cells express the Vβ5 gene product in the β subunit of the TcR, while Jurkat cells express Vβ8. Vβ expression in primary T cells isolated from buffy coats is heterogeneous. Primary T cell populations expressing specific Vβ epitopes in the TcR were generated by plating CD3+ T cells on Vβ-specific antibody-coated flasks or by positive immunomagnetic selection. Immunotoxins directed against the invariant CD3ϵ epitope target and kill all T cells. Immunoconjugates targeted at distinct anti-Vβ epitopes are specific for cells that express the corresponding gene product in the TcR. The results demonstrate the ability of antiTcR-based immunotoxins selectively to kill T cells with defined Vβ epitopes. These reagents may be clinically useful in disorders mediated by autoreactive T cell populations exhibiting Vβ restriction and in the treatment of clonal TcR-expressing lymphomas.