Selective killing of T cells by immunotoxins directed at distinct Vβ epitopes of the T cell receptor

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-CD3? or distinct anti-V_β 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 V_β5 gene product in the β subunit of the TcR, while Jurkat cells express V_β8. V_β expression in primary T cells isolated from buffy coats is heterogeneous. Primary T cell populations expressing specific V_β epitopes in the TcR were generated by plating CD3⁺ T cells on V_β-specific antibody-coated flasks or by positive immunomagnetic selection. Immunotoxins directed against the invariant CD3? epitope target and kill all T cells. Immunoconjugates targeted at distinct anti-V_β 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 V_β epitopes. These reagents may be clinically useful in disorders mediated by autoreactive T cell populations exhibiting V_β restriction and in the treatment of clonal TcR-expressing lymphomas.