Selective killing of T cells by immunotoxins directed at distinct V beta 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 beta 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 beta 5 gene product in the beta subunit of the TcR, while Jurkat cells express V beta 8. V beta expression in primary T cells isolated from buffy coats is heterogeneous. Primary T cell populations expressing specific V beta epitopes in the TcR were generated by plating CD3+ T cells on V beta-specific antibody-coated flasks or by positive immunomagnetic selection. Immunotoxins directed against the invariant CD3 epsilon epitope target and kill all T cells. Immunoconjugates targeted at distinct anti-V beta epitopes are specific for cells that express the corresponding gene product in the TcR. The results demonstrate the ability of anti-TcR-based immunotoxins selectively to kill T cells with defined V beta epitopes. These reagents may be clinically useful in disorders mediated by autoreactive T cell populations exhibiting V beta restriction and in the treatment of clonal TcR-expressing lymphomas.
Rigaut
K D
KD
Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, MD 20892, USA.
Scharff
J E
JE
Neville
D M
DM
D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D002460:Cell Line; D000939:Epitopes; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D000922:Immunotoxins; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion / Q000379:methods*; D014176:Protein Biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D000922:Immunotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta