Targeting cytotoxic T cells to antigen-specific B lymphocytes

✍ Scribed by Hans-Georg Rammensee; Michael H. Julius; David Nemazee; Jean Langhorne; Rinus Lamers; Georges Köhler

• Publisher: John Wiley and Sons
• Year: 1987
• Tongue: English
• Weight: 368 KB
• Volume: 17
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830170322

✦ Synopsis

Targeting cytotoxic T cells to antigen-specific B lymphocytes

A recent development in immunomanipulation involves the targeting of cytotoxic T lymphocytes (CTL) to cell-bound antigens using bispecific antibodies. These antibodies have been engineered such that specificity is directed against the T cell receptor (TCR) or TCR-associated T3 molecules, as well as against the chosen antigen. The present study was aimed to force interactions between T and B cells by bridging their receptors. F23.1 antibodies, which are specific for gene products of the TCR V,8 gene family, were conjugated with TNP (2,4,6-trinitrophenyl) and this construct was used to bridge the receptors of Vp8' T cells with the receptors of TNP-specific B cells. The bridging was demonstrated by direct killing of both a TNP-specific B hybridoma and of blast cells from mice transgenic for p,x of the TNP-specific antibody Sp6. Further, F23.1-TNP constructs in conjunction with V68' CTL were shown to specifically deplete Ig-secreting B cells from Sp6 transgenic mice. Conjugates of TCRspecific antibodies and antigen are theoretically useful in vivo to either deplete or expand B cells of a given specificity by coupling their receptors to the TCR of CTL or T helper cells, respectively.